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Çelik NGK, Altınboğa AA, Ünal TDK. Micronucleus and Nuclear Budding Help to Identify Malignancy in Thyroid Fine Needle Aspiration Cytology. Cytopathology 2025. [PMID: 40281679 DOI: 10.1111/cyt.13505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/04/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025]
Abstract
OBJECTIVE Micronucleus (MN) and Nuclear Budding (NB) Have Been Used as an Important Stimulus for Nuclear Atypia in Revealing Chromosomal Damage and Cancer Risk. This Study Aims to Assess MN and NB as Nuclear Parameters and Explore Their Role in Differential Diagnosis of Thyroid FNA and "Bethesda System for Reporting Thyroid Cytology" (BSRTC). METHODS The Study Included 350 Thyroid FNA Samples Categorised According to BSRTC. NB And MN Were Evaluated in 1000 Thyrocytes on FNA Slides. The Thyroidectomy Sections Were Divided Into Three Categories as 'Malignant', 'Low-Risk' and 'Benign'. RESULTS A Total of 350 Cases Were Classified as follows: 55 (15.71%) Benign, 159 (45.43%) Atypia of Undetermined Significance (AUS), 20 (5.71%) Follicular Neoplasm (FN), 48 (13.71%) Suspicious for Malignancy (SFM) and 68 (19.43%) Malignant. In comparison to all other cytopathologic diagnostic groups, the benign group had significantly lower levels of MN and NB (p < 0.001). The AUS group's MN and NB counts were significantly lower than those of the FN, SFM and malignant groups (MN for AUS-FN/SFM/M p < 0.001, NB for AUS-FN p = 0.01, NB for AUS-SFM/M p < 0.001, respectively). MN and NB counts were greater in the AUS group for cases with a malignant histopathologic diagnosis than for those with a benign histopathologic diagnosis (p < 0.001). MN and NB cut-off values > 5.50 and > 14.50, respectively, suggest high sensitivity and specificity of malignancy. CONCLUSIONS Increased Frequency of MN and NB closely associated with an increased risk of malignancy in thyroid FNA. Assessing MN and NB in thyroid FNA may help better stratify the risk in the AUS category.
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Affiliation(s)
| | - Ayşegül Aksoy Altınboğa
- Department of Pathology, Ankara Bilkent City Hospital, Ankara, Turkey
- Department of Pathology, Medical Faculty, Ankara Yildirim Beyazit University, Ankara, Turkey
| | - Tuba Dilay Kökenek Ünal
- Department of Pathology, Ankara Bilkent City Hospital, Ankara, Turkey
- Department of Pathology, Medical Faculty, Ankara Yildirim Beyazit University, Ankara, Turkey
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Tiwana KK, Kaur M, Goyal S, Bhandhari L. The role of micronucleus scoring in cervical papanicolaou smears: A 1-year study. Ann Afr Med 2022; 21:355-360. [PMID: 36412334 PMCID: PMC9850894 DOI: 10.4103/aam.aam_87_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Aims and Objectives To compare the micronucleus (MN) score in all the major diagnostic categories as per "The Bethesda System for Reporting Cervical Cytology" 2014 including negative for intraepithelial lesions and malignancy (NILM), inflammatory, abnormal squamous cells of undetermined significance (ASC-US), abnormal squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H), low-grade squamous intraepithelial lesion (LSIL), HSIL, and invasive carcinoma (IC) and to assess the role of MN scoring as a biomarker for predicting risk of carcinoma. Materials and Methods A total of 1000 conventional cervical smears stained with Papanicolaou (Pap) stain, comprising unsatisfactory for evaluation (86), NILM (140), inflammatory (696), ASC-US (23), ASC-H (16), LSIL (18), HSIL (15), and IC (6) were studied independently by two pathologists, and the number of MN cells per 1000 epithelial cells in high-power (×400) and oil immersion (×1000) was counted and expressed as MN score per 1000 cells. Results The mean MN score ± standard deviation was found to be 0.99 ± 0.744 in NILM cases, 0.67 ± 0.782 in inflammatory cases, 1.57 ± 0.507 in ASC-US cases, 1.63 ± 0.50 in ASC-H cases, 1.56 ± 0.511 in LSIL cases, 2.47 ± 0.516 in HSIL cases, and 3.0 ± 0.00 in IC cases. A step-wise increase was observed in MN score from inflammatory to IC categories. Conclusions MN score is a reliable and easy test that can be used in conjunction with routine cervical PAP to assess the risk of malignant transformation in the uterine cervix as a biomarker for predicting the risk of carcinoma.
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Affiliation(s)
| | - Mohanvir Kaur
- Department of Pathology, Government Medical College, Patiala, Punjab, India,Address for correspondence: Dr. Mohanvir Kaur, #38, Joginder Nagar, Patiala, Punjab, India. E-mail:
| | - Shaina Goyal
- Department of Pathology, Government Medical College, Patiala, Punjab, India
| | - Lachhima Bhandhari
- Department of Pathology, Government Medical College, Patiala, Punjab, India
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Warke DJ, Khot KP. A comparative study for qualitative and quantitative analysis of light and fluorescence microscopy stains in oral premalignant and malignant lesions. Cytojournal 2021; 18:14. [PMID: 34221103 PMCID: PMC8247698 DOI: 10.25259/cytojournal_39_2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 05/28/2021] [Indexed: 11/07/2022] Open
Abstract
Objectives: The present study highlights the use and benefit of fluorescence microscopy stains in easy diagnosis of oral premalignant and malignant lesions. This study was carried out to evaluate the efficiency of light microscopy using Papanicolaou stain (PAP) and May Grunwald Giemsa (MGG) stains and fluorescence microscopy using acridine orange (AO) and 4′,6-diamidino-2-phenyl indole (DAPI) stains. All smears have been qualitatively and quantitatively analyzed in premalignant and malignant lesions using cytology and cytomorphometry. Materials and Methods: The subjects included in this study were selected from patients suffering from premalignant and clinically suspicious malignant lesions. Specimens were collected from the most representative site in study groups and normal buccal mucosa in the control group. The smears were evaluated under fluorescence microscopy for AO and DAPI and under light microscopy for conventional PAP and MGG. We studied 5 HPF to compare the number of normal cells to dysplastic cells. These were then subjected for cytomorphometric and statistical analysis. Results: Assessment of quality using quality index revealed that PAP has better diagnostic efficiency as compared to MGG because the quality index of PAP was 0.87 and that of MGG was 0.74, the quality index of AO was 0.9, and that of DAPI was found to be 0.82, hence proving AO to be better in comparison with DAPI. Conclusion: We found that among all the four stains used AO is reliable, has greater efficacy, and can be easily performed with less cost. Despite the difficulties mentioned in this study, the progress in the field of fluorescence microscopy is expected to be rapid in the following years.
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Affiliation(s)
- Darshana Jayant Warke
- Department of Oral and Maxillofacial Pathology, Vedantaa Institute of Medical Sciences, Mumbai, Maharashtra, India
| | - Komal Paresh Khot
- Department of Oral Pathology, YMT Dental College, Mumbai, Maharashtra, India
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Impact of infections, preneoplasia and cancer on micronucleus formation in urothelial and cervical cells: A systematic review. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2020; 787:108361. [PMID: 34083051 DOI: 10.1016/j.mrrev.2020.108361] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 12/03/2020] [Accepted: 12/05/2020] [Indexed: 11/24/2022]
Abstract
Approximately 165,000 and 311,000 individuals die annually from urothelial (UC) and cervical (CC) cancer. The therapeutic success of these cancers depends strongly on their early detection and could be improved by use of additional diagnostic tools. We evaluated the current knowledge of the use of micronucleus (MN) assays (which detect structural and numerical chromosomal aberrations) with urine- (UDC) and cervix-derived (CDC) cells for the identification of humans with increased risks and for the diagnosis of UC and CC. Several findings indicate that MN rates in UDC are higher in individuals with inflammation and schistosomiasis that are associated with increased prevalence of UC; furthermore, higher MN rates were also found in CDC in women with HPV, Candidiasis and Trichomonas infections which increase the risks for CC. Only few studies were published on MN rates in UDS in patients with UC, two concern the detection of recurrent bladder tumors. Strong correlations were found in individuals with abnormal CC cells that are scored in Pap tests and histopathological abnormalities. In total, 16 studies were published which concerned these topics. MN rates increased in the order: inflammation < ASC-US/ASC-H < LSIL < HSIL < CC. It is evident that MNi numbers increase with the risk to develop CC and with the degree of malignant transformation. Overall, the evaluation of the literature indicates that MNi are useful additional biomarkers for the prognosis and detection of CC and possibly also for UC. In regard to the diagnosis/surveillance of UC, further investigations are needed to draw firm conclusions, but the currently available data are promising. In general, further standardization of the assays is needed (i.e. definition of optimal cell numbers and of suitable stains as well as elucidation of the usefulness of parameters reflecting cytotoxicity and mitotic activity) before MN trials can be implemented in routine screening.
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Nersesyan A, Muradyan R, Kundi M, Fenech M, Bolognesi C, Knasmueller S. Smoking causes induction of micronuclei and other nuclear anomalies in cervical cells. Int J Hyg Environ Health 2020; 226:113492. [PMID: 32088596 DOI: 10.1016/j.ijheh.2020.113492] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 02/03/2020] [Accepted: 02/13/2020] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Smoking is an independent cause of cervical cancer, which is the 4th most common malignancy in women. It is currently not known if tobacco consumption causes chromosomal damage (which is a hallmark of human cancer) in cervical cells and if age and the hormonal status have an impact on tobacco induced genetic instability in the cervix. METHODS We conducted a study with pre- and post-menopausal women smokers and never-smokers (25/group). Smokers consumed 30 light/medium cigarettes/day and were matched with the non-smoking group. Cervical cells were analyzed for induction of micronuclei (MN) which are caused by structural/numerical chromosomal aberrations; additionally, other nuclear anomalies reflecting genomic instability and cytotoxicity were scored. Furthermore, the frequencies of basal cells were recorded which reflect the mitotic activity of the mucosa. RESULTS MN and other abnormalities were increased in both groups of smokers. The effects were most pronounced in postmenopausal smokers (i.e. 2-fold higher) compared to premenopausal smokers. Also the number of basal cells (indicative for cell proliferation) was clearly enhanced in older women. Tar and nicotine had no detectable impact on chromosomal damage but a clear association with pack-years was observed. CONCLUSIONS Smoking increased chromosomal instability, cytotoxicity and induced cell divisions in cervical mucosa cells of pre- and post-menopausal women. The effects were more pronounced in the latter group indicating a higher risk for diseases (including cancer) that are causally related to DNA damage.
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Affiliation(s)
- Armen Nersesyan
- Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
| | | | - Michael Kundi
- Center for Public Health, Medical University of Vienna, Vienna, Austria.
| | | | - Claudia Bolognesi
- Environmental Carcinogenesis Unit, Ospedale Policlinico San Martino, Genoa, Italy.
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Bonassi S, Fenech M. Micronuclei and Their Association with Infertility, Pregnancy Complications, Developmental Defects, Anaemias, Inflammation, Diabetes, Chronic Kidney Disease, Obesity, Cardiovascular Disease, Neurodegenerative Diseases and Cancer. THE MICRONUCLEUS ASSAY IN TOXICOLOGY 2019. [DOI: 10.1039/9781788013604-00038] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Micronuclei (MN) are a strong cytogenetic indicator of a catastrophic change in the genetic structure and stability of a cell because they originate from either chromosome breaks or whole chromosomes that have been lost from the main nucleus during cell division. The resulting genetic abnormalities can to lead to cellular malfunction, altered gene expression and impaired regenerative capacity. Furthermore, MN are increased as a consequence of genetic defects in DNA repair, deficiency in micronutrients required for DNA replication and repair and exposure to genotoxic chemicals and ultraviolet or ionising radiation. For all of these reasons, the measurement of MN has become one of the best-established methods to measure DNA damage in humans at the cytogenetic level. This chapter is a narrative review of the current evidence for the association of increased MN frequency with developmental and degenerative diseases. In addition, important knowledge gaps are identified, and recommendations for future studies required to consolidate the evidence are provided. The great majority of published studies show a significant association of increased MN in lymphocytes and/or buccal cells with infertility, pregnancy complications, developmental defects, anaemias, inflammation, diabetes, cardiovascular disease, kidney disease, neurodegenerative diseases and cancer. However, the strongest evidence is from prospective studies showing that MN frequency in lymphocytes predicts cancer risk and cardiovascular disease mortality.
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Vargas-Rondón N, Villegas VE, Rondón-Lagos M. The Role of Chromosomal Instability in Cancer and Therapeutic Responses. Cancers (Basel) 2017; 10:cancers10010004. [PMID: 29283387 PMCID: PMC5789354 DOI: 10.3390/cancers10010004] [Citation(s) in RCA: 116] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Revised: 12/22/2017] [Accepted: 12/25/2017] [Indexed: 12/31/2022] Open
Abstract
Cancer is one of the leading causes of death, and despite increased research in recent years, control of advanced-stage disease and optimal therapeutic responses remain elusive. Recent technological improvements have increased our understanding of human cancer as a heterogeneous disease. For instance, four hallmarks of cancer have recently been included, which in addition to being involved in cancer development, could be involved in therapeutic responses and resistance. One of these hallmarks is chromosome instability (CIN), a source of genetic variation in either altered chromosome number or structure. CIN has become a hot topic in recent years, not only for its implications in cancer diagnostics and prognostics, but also for its role in therapeutic responses. Chromosomal alterations are mainly used to determine genetic heterogeneity in tumors, but CIN could also reveal treatment efficacy, as many therapies are based on increasing CIN, which causes aberrant cells to undergo apoptosis. However, it should be noted that contradictory findings on the implications of CIN for the therapeutic response have been reported, with some studies associating high CIN with a better therapeutic response and others associating it with therapeutic resistance. Considering these observations, it is necessary to increase our understanding of the role CIN plays not only in tumor development, but also in therapeutic responses. This review focuses on recent studies that suggest possible mechanisms and consequences of CIN in different disease types, with a primary focus on cancer outcomes and therapeutic responses.
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Affiliation(s)
- Natalia Vargas-Rondón
- School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia.
| | - Victoria E Villegas
- Biology Program, Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 111221, Colombia.
| | - Milena Rondón-Lagos
- School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia.
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Benvindo-Souza M, Assis RA, Oliveira EAS, Borges RE, Santos LRDS. The micronucleus test for the oral mucosa: global trends and new questions. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2017; 24:27724-27730. [PMID: 29152700 DOI: 10.1007/s11356-017-0727-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 11/08/2017] [Indexed: 06/07/2023]
Abstract
This study reviews global trends in the publication of papers on the micronucleus test of the exfoliated cells of the oral mucosa in mammals as an approach for environmental biomonitoring. This test has been widely used due to its precision for the detection of chromosome damage. Our temporal analysis showed a significant increase (p < 0.05) in the publication of papers on the oral mucosa over the past 33 years. Brazil was the country that published most papers (24% of the total), followed by India (16%), the USA (10%), Mexico (7%), and Turkey (6%). A further 30 countries contributed the other 37% of the papers. Overall, 99% of the micronucleus studies involved human subjects, and only 1% involved other mammals. As many wild mammals are subject to the same environmental pressures as humans, in particular chemical pollution, it seems likely that many species are equally susceptible to genotoxicogical damage. We emphasize the importance of applying this technique to the analysis of the oral mucosa of wild mammals, as well as the evaluation of its effectiveness, as observed in humans, and the expansion of the available approaches to the monitoring of environmental quality.
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Affiliation(s)
- Marcelino Benvindo-Souza
- Laboratório de Biologia Animal, Instituto Federal Goiano, IF Goiano, Rodovia Sul Goiana, Km 01, Zona Rural, Rio Verde, GO, CEP 75.901-970, Brazil
| | - Rhayane Alves Assis
- Laboratório de Biologia Animal, Instituto Federal Goiano, IF Goiano, Rodovia Sul Goiana, Km 01, Zona Rural, Rio Verde, GO, CEP 75.901-970, Brazil
| | - Eliane Andreia Santos Oliveira
- Laboratório de Biologia Animal, Instituto Federal Goiano, IF Goiano, Rodovia Sul Goiana, Km 01, Zona Rural, Rio Verde, GO, CEP 75.901-970, Brazil
| | - Rinneu Elias Borges
- Departamento de Biologia, Universidade de Rio Verde, UniRV, Fazenda Fontes do Saber, Rio Verde, GO, CEP: 75.901-970, Brazil
| | - Lia Raquel de Souza Santos
- Laboratório de Biologia Animal, Instituto Federal Goiano, IF Goiano, Rodovia Sul Goiana, Km 01, Zona Rural, Rio Verde, GO, CEP 75.901-970, Brazil.
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Kokenek-Unal TD, Coban I. Micronuclei and nuclear buds: Highlighting overlooked indicators of chromosomal damage in thyroid aspiration smears. Diagn Cytopathol 2017; 45:673-680. [PMID: 28440063 DOI: 10.1002/dc.23738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Revised: 03/26/2017] [Accepted: 04/11/2017] [Indexed: 11/07/2022]
Abstract
BACKGROUND We aimed to examine the diagnostic utility of micronuclei (MN) and nuclear buds (NBs) in aspiration smears of the well-differentiated epithelial lesions of thyroid. METHODS One hundred five cases composed of 34 follicular nodular disease (FND), 31 Hashimoto's thyroiditis (HT), and 40 papillary thyroid carcinoma (PTC) were compiled retrospectively. May- Grünwald Giemsa (MGG) stained smears of each case were selected to count cells with nuclear protrusions (NPs) per 1000 cells. The frequency of cells with NPs (MN&NBs) was compared by using Mann-Whitney U test and Kruskal-Wallis tests when appropriate. Post-Hoc Tukey test was used for pairwise comparison of different diagnostic categories. By running a ROC curve analysis, diagnostic usefulness of the frequency of cells with NPs (MN&NBs) and their cut-off values to predict malignant behavior were calculated. P < 0.05 was regarded as significant. RESULTS NPs (MN&NBs) were significantly more frequent in malignant cases than benign ones. NBs were more frequent in conventional PTC compared to FV of PTC, but the frequency of MN did not significantly differ between these. ROC curve analysis revealed that evaluation of the frequency of cells with NPs (MN&NBs) was a highly specific, sensitive, and diagnostically useful method to identify malignant behavior. CONCLUSION To the best of our knowledge, this is the first study in the literature to evaluate the frequency of cells with NPs (MN&NBs) in human thyroid aspiration smears. Our results show that evaluation of NPs (MN&NBs) may be a useful diagnostic tool to detect PTC in thyroid aspiration smears. Diagn. Cytopathol. 2017;45:673-680. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Tuba Dilay Kokenek-Unal
- Department of Pathology, Kayseri Research and Training Hospital, University of Health Sciences, Istanbul, Turkey
| | - Ipek Coban
- Department of Pathology, Gayrettepe Florence Nightingale Hospital, Istanbul Bilim University, Istanbul, Turkey
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Roy P, Mukherjee A, Giri S. Evaluation of genetic damage in tobacco and arsenic exposed population of Southern Assam, India using buccal cytome assay and comet assay. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2016; 124:169-176. [PMID: 26517729 DOI: 10.1016/j.ecoenv.2015.10.019] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 10/13/2015] [Accepted: 10/15/2015] [Indexed: 06/05/2023]
Abstract
Ground water is the principal source of drinking water in Assam. Ground water contamination of arsenic in drinking water is a great concern for human health and considered as a human carcinogen. The present cytogenetic biomonitoring study was undertaken to investigate the genotoxic effects associated with people of southern Assam consuming arsenic contaminated water and chewing tobacco. Employing the buccal cytome assay, exfoliated cells were analyzed in 138 individuals of age range 22-42 years and divided into four groups. Group I (n=54) are participants residing in localities where ground water contains arsenic concentration below the permissible limit (<10μg/l) and without any tobacco chewing history. Group II (n=32) participants from the same area but they are tobacco chewers. Group III (n=24) participants from localities where significantly high arsenic contamination in ground water were observed. Whereas the Group IV (n=28) consists of participants from the arsenic contaminated area and also tobacco chewers. Body mass index (BMI) in all the groups are found to be nearly same and in normal range. Statistically significant (P<0.001) increase in genotoxic, cell death parameters and cell proliferation biomarkers were observed in the Group IV compared to other groups. In the comet assay, percent of tail DNA gradually increases among the groups and has statistical significance. Spearman correlation revealed strong positive correlation between the arsenic exposed peoples and the binucleated cells (r=0.4763; P<0.001). Amount of chewing tobacco had significant positive correlation with micronucleus frequency (r=0.268; P<0.05) and karyolitic cells (r=0.217; P<0.05) and also in the percentage of tail DNA (r=0.5532, P<0.001). A statistically significant increase in glucose content and decrease in hemoglobin content as well as acetylcholine esterase in the blood of exposed individuals was observed. Our preliminary study indicate that population exposed to arsenic through drinking water may become more susceptible towards chewing tobacco induced nuclear damage as evaluated by buccal cytome assay and comet assay.
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Affiliation(s)
- Prasenjit Roy
- Laboratory of Genetic Toxicology and Environmental Health, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India.
| | - Anita Mukherjee
- Laboratory of Cell Biology and Genetic Toxicology, Department of Genetics, Ballygunge Science College, University of Calcutta, Kolkata, India
| | - Sarbani Giri
- Laboratory of Genetic Toxicology and Environmental Health, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India
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da Silva VHP, de Moura CFG, Ribeiro FAP, Cesar A, Pereira CDS, Silva MJD, Vilegas W, Ribeiro DA. Genotoxicity and cytotoxicity induced by municipal effluent in multiple organs of Wistar rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2014; 21:13069-13080. [PMID: 24996946 DOI: 10.1007/s11356-014-3261-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Accepted: 06/24/2014] [Indexed: 06/03/2023]
Abstract
The aim of this study was to evaluate cytotoxicity and genotoxicity in multiple organs of rats induced by municipal effluent released by submarine outfall in city of Santos. A total of 20 male Wistar rats were exposed to effluents by drinking water ad libitum at concentrations of 0, 10, 50, and 100 % for 30 days. Microscopic analysis revealed severe lesions such as necrosis and hemorrhagic areas in liver and kidney from animals exposed to effluent at 50 and 100 % concentration. DNA damage in peripheral blood, liver, and kidney cells were detected by comet assay at higher concentrations of effluent. Moreover, a decrease DNA repair capacity was detected in liver cells. Significant statistical differences (p<0.05) for micronucleated cells from liver were noticed at 50 % concentration of effluent. Taken together, our results demonstrate that municipal effluent is able to induce cytotoxicity and genotoxicity in multiple organs of Wistar rats.
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Affiliation(s)
- Victor Hugo Pereira da Silva
- Department of Biosciences, Federal University of Sao Paulo, UNIFESP, Av. Ana Costa 95, 11060-001, Santos, SP, Brazil
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Chinde S, Kumari M, Devi KR, Murty US, Rahman MF, Kumari SI, Mahboob M, Grover P. Assessment of genotoxic effects of lead in occupationally exposed workers. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2014; 21:11469-11480. [PMID: 24906834 DOI: 10.1007/s11356-014-3128-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 05/28/2014] [Indexed: 06/03/2023]
Abstract
The genotoxicological effects in 200 lead acid storage battery recycling and manufacturing industry workers in Hyderabad along with matched 200 controls were studied. The genetic damage was determined by comet, micronucleus (MN), and chromosomal aberration (CA) test in peripheral blood lymphocytes (PBL). The MN test was also carried out in buccal epithelial cells (BECs). Pb in ambient air, blood Pb (B-Pb) concentrations, and hematological parameters were measured. The superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and malondialdehyde (MDA) formed were also studied. The results of the present study showed that there was a statistically significant (P < 0.01) increase in mean percent tail DNA, frequency of CA, and MN in PBL as well as in BEC as compared to controls. Pb in ambient air and B-Pb concentrations were found to be significantly higher (P < 0.01). The hematocrit, hemoglobin, and red blood cell values were significantly lowered in Pb-exposed workers in comparison to controls. SOD, GPx, and CAT levels were significantly decreased while GSH and MDA levels increased in exposed group when compared to control group. The present study suggests that environmental health standards should be enforced to control Pb contamination from battery industries to reduce human health risk.
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Affiliation(s)
- Srinivas Chinde
- Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh, 500007, India
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Bueno CT, Silva CMDD, Barcellos RB, Silva JD, Santos CRD, Menezes JES, Menezes HS, Rossetti MLR. Association between cervical lesion grade and micronucleus frequency in the Papanicolaou test. Genet Mol Biol 2014; 37:496-9. [PMID: 25249771 PMCID: PMC4171763 DOI: 10.1590/s1415-47572014000400004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2014] [Accepted: 04/10/2014] [Indexed: 11/22/2022] Open
Abstract
The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal.
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Cassel APR, Barcellos RB, da Silva CMD, de Matos Almeida SE, Rossetti MLR. Association between human papillomavirus (HPV) DNA and micronuclei in normal cervical cytology. Genet Mol Biol 2014; 37:360-3. [PMID: 25071400 PMCID: PMC4094606 DOI: 10.1590/s1415-47572014005000010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Accepted: 03/20/2014] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to investigate the association between HPV-DNA and micronucleus (MN) frequency in women with normal cervical cytology. A total of 158 normal cervical smears were analyzed cytologically. The HPV genome was amplified using the GP5+/bioGP6+ consensus primers. HPV-DNA of high-risk types 16, 18, 31, 33, 39, 45 and 59 were also investigated. Of the 158 samples, 20 (12.7%) and 47 (29.7%) were positive for HPV-DNA and MN, respectively. Evidence for MN was found in 11 out of 20 (55%) HPV-DNA positive samples and in 36 out of 138 (26.1%) HPV-DNA negative ones. MN presence was significantly higher in HPV-DNA positive samples (p = 0.016). On the other hand, the absence of MN observed in a considerable number of HPV-DNA negative samples (102) may be of great value in predicting the absence of HPV. The mean age of HPV-DNA positive women (34.2 ± 12.6) was significantly lower than the mean age of HPV-DNA negative women (43.9 ± 13.7) (p = 0.003). Infection by one or multiple HPV types was found in 11 out of 20 (55.0%) and 9 out of 20 (45.0%) samples, respectively. The evaluation of MN using cervical smears collected for cytology tests could, thus, be used as additional information to monitor a population’s exposure to HPV.
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Affiliation(s)
- Ana Paula Rebelo Cassel
- Programa de Pós-Graduação em Genética e Toxicologia Aplicada , Universidade Luterana do Brasil , Canoas, RS , Brazil
| | - Regina Bones Barcellos
- Centro de Desenvolvimento Científico e Tecnológico , Fundação Estadual de Produção e Pesquisa em Saúde , Porto Alegre, RS , Brazil
| | - Cláudia Maria Dornelles da Silva
- Centro de Desenvolvimento Científico e Tecnológico , Fundação Estadual de Produção e Pesquisa em Saúde , Porto Alegre, RS , Brazil
| | - Sabrina Esteves de Matos Almeida
- Centro de Desenvolvimento Científico e Tecnológico , Fundação Estadual de Produção e Pesquisa em Saúde , Porto Alegre, RS , Brazil . ; Instituto da Saúde , Universidade Feevale , Novo Hamburgo, RS , Brazil
| | - Maria Lucia Rosa Rossetti
- Programa de Pós-Graduação em Genética e Toxicologia Aplicada , Universidade Luterana do Brasil , Canoas, RS , Brazil . ; Centro de Desenvolvimento Científico e Tecnológico , Fundação Estadual de Produção e Pesquisa em Saúde , Porto Alegre, RS , Brazil
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Cortés-Gutiérrez EI, Dávila-Rodríguez MI, Cerda-Flores RM. Chromosomal damage as prognosis marker in cervical carcinogenesis. CYTOL GENET+ 2014. [DOI: 10.3103/s0095452714030049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Avanzi S, Alvisi G, Ripalti A. How virus persistence can initiate the tumorigenesis process. World J Virol 2013; 2:102-9. [PMID: 24175234 PMCID: PMC3785046 DOI: 10.5501/wjv.v2.i2.102] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Revised: 04/04/2013] [Accepted: 04/10/2013] [Indexed: 02/05/2023] Open
Abstract
Human oncogenic viruses are defined as necessary but not sufficient to initiate cancer. Experimental evidence suggests that the oncogenic potential of a virus is effective in cells that have already accumulated a number of genetic mutations leading to cell cycle deregulation. Current models for viral driven oncogenesis cannot explain why tumor development in carriers of tumorigenic viruses is a very rare event, occurring decades after virus infection. Considering that viruses are mutagenic agents per se and human oncogenic viruses additionally establish latent and persistent infections, we attempt here to provide a general mechanism of tumor initiation both for RNA and DNA viruses, suggesting viruses could be both necessary and sufficient in triggering human tumorigenesis initiation. Upon reviewing emerging evidence on the ability of viruses to induce DNA damage while subverting the DNA damage response and inducing epigenetic disturbance in the infected cell, we hypothesize a general, albeit inefficient hit and rest mechanism by which viruses may produce a limited reservoir of cells harboring permanent damage that would be initiated when the virus first hits the cell, before latency is established. Cells surviving virus generated damage would consequently become more sensitive to further damage mediated by the otherwise insufficient transforming activity of virus products expressed in latency, or upon episodic reactivations (viral persistence). Cells with a combination of genetic and epigenetic damage leading to a cancerous phenotype would emerge very rarely, as the probability of such an occurrence would be dependent on severity and frequency of consecutive hit and rest cycles due to viral reinfections and reactivations.
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Gayathri B, Kalyani R, Hemalatha A, Vasavi B. Significance of micronucleus in cervical intraepithelial lesions and carcinoma. J Cytol 2013; 29:236-40. [PMID: 23326026 PMCID: PMC3543591 DOI: 10.4103/0970-9371.103941] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background: The micronuclei (MNi) test on exfoliated cells has been successfully used to screen population groups at risk for cancers of oral cavity, urinary bladder, cervix and esophagus. Their frequency appears to increase in carcinogen-exposed tissues long before any clinical symptoms are evident. There are only limited numbers of studies on MN scoring in cervical pre-neoplastic and neoplastic conditions. Aims: To compare the micronucleus (MN) score in the whole spectrum of cervical lesions including normal, inflammatory, abnormal squamous cells of undetermined significance (ASC-US), abnormal squamous cells cannot exclude HSIL (ASC-H), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and invasive cancer (IC) and to evaluate the role of MN as a biomarker in different pre-neoplastic and neoplastic lesions. Materials and Methods: A total of 221 slides, comprised of normal (32), inflammatory (32), ASC-US (31), ASC-H (31), LSIL (32), HSIL (31) and IC (32), were studied. All the cases were reviewed by two pathologists independently. Histopathological correlation was done in a few cases of ASC-US, ASC-H, HSIL and IC which were available in the department. Two observers separately and independently counted the number of micronucleated cells per 1,000 epithelial cells in oil immersion magnification and were expressed as MN score per 1,000 cells. Results: The mean MN scores ± SD in normal, inflammatory, ASC-US, ASC-H, LSIL, HSIL and IC cases of cervical lesions were 0.84±0.68, 1.06±0.84, 3±0.73, 4.78±1.43, 4.06±1.13, 8.03±1.64 and 10.5±2.01, respectively. MN scores of IC and HSIL were significantly high compared to normal (P<0.000), inflammatory (P<0.000), ASC-US (P<0.000), ASC-H (P<0.000) and LSIL (P<0.000) group (analysis of variance test). LSIL showed significant difference with the normal (P<0.000), inflammatory (P=0.001), ASC-US (P=0.028), HSIL (P<0.000) and IC (<0.000), but not with the ASC-H (P=0.64) group. Conclusions: MN scoring on the epithelial cells of cervix could be used as a biomarker in cancer screening. This is an easy, simple, reliable, reproducible and objective test which can be performed on routinely stained pap smears.
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Affiliation(s)
- Bn Gayathri
- Department of Pathology, Sri Devaraj Urs Medical College, Tamaka, Kolar, Karnataka, India
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Bhatia A, Kumar Y. Cancer cell micronucleus: an update on clinical and diagnostic applications. APMIS 2012; 121:569-81. [PMID: 23278233 DOI: 10.1111/apm.12033] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Accepted: 10/25/2012] [Indexed: 12/15/2022]
Abstract
Micronucleus (MN) is the small nucleus that forms whenever a chromosome or its fragment is not incorporated into one of the daughter nuclei during cell division. Any form of genotoxic stress due to extraneous or internal factors leads to formation of a MN, which serves as an indicator of chromosomal instability. Chromosomal damage and formation of MN are believed to play a significant role in the pathogenesis of many malignancies. Studies have shown that MN assay can be used as a tool for risk prediction, screening, diagnosis, prognosis and as a treatment-response indicator in cancers. With the advancements in technology, greater details are becoming available regarding the molecular events in carcinogenesis. The micronuclei (MNi) in the cancer cells are now being used as tools to understand the pathogenetics of the malignancies. However, despite large number of studies on MNi in lymphocytes or exfoliated cells of cancer patients, the data regarding a cancer cell MN remain scarce. This review article tries to unleash some of the mysteries related to the formation of MN inside the cancer cell. Also, it discusses the possible effects and the events post MN formation in the cancer cell.
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Affiliation(s)
- Alka Bhatia
- Department of Experimental Medicine & Biotechnology, PGIMER, Chandigarh, India.
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Wen CH, Lin CH, Tsao SC, Su YC, Tsai MH, Chai CY. Micronucleus scoring in liver fine needle aspiration cytology. Cytopathology 2012; 24:391-5. [PMID: 22974178 DOI: 10.1111/cyt.12009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVE This study evaluated the role of the micronucleus (MN) in liver fine needle aspiration (FNA) cytology. METHODS Histological features of 75 cases of hepatocellular carcinoma (HCC), of which 25 were well differentiated, 37 moderately differentiated and 13 poorly differentiated, and 58 benign hepatic lesions (total, 133 cases) were correlated with MN expression observed in FNA smears reported as benign (n =40), atypical (n = 14), suspicious (n = 30) and malignant (n =49). RESULTS Stepwise increases in the MN score (0.4 ± 0.6, 1.2 ± 1.3, 6.3 ± 4.2 and 14.8 ± 8.8) correlated with the degree of cytological abnormality: benign, atypia, suspicious and malignant, respectively. The mean MN scores for well-, moderately and poorly differentiated HCC were 5.4 ± 2.2, 11.5 ± 4.5 and 24.9 ± 9.1, respectively, which was significantly different between malignant and suspicious (P < 0.0001), between suspicious and atypical (P= 0.008) but not between atypical and benign. The MN scores differed significantly between all degrees of differentiation of HCC and between the HCC and benign hepatic lesions (P < 0.0001). High sensitivity, specificity and accuracy of liver FNA for diagnosing HCC (96%, 98%, and 96%, respectively) were obtained at a cutoff of three for the MN score. CONCLUSIONS The MN score is an effective HCC biomarker and has a good potential use as an ancillary tool for diagnosing HCC using FNA cytology.
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Affiliation(s)
- C-H Wen
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDepartment of Pathology, Foo-Yin University Hospital, Ping-Tong Hsien, TaiwanGraduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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MILOŠEVIĆ-DJORDJEVIĆ OLIVERA, STOŠIĆ IVANA, GRUJIČIĆ DARKO, BANKOVIĆ DRAGIĆ, ARSENIJEVIĆ SLOBODAN. Cervical precancerous lesions - chromosomal instability in peripheral blood lymphocytes in relation to lesion stage, age and smoking habits. Acta Obstet Gynecol Scand 2011; 90:1082-7. [DOI: 10.1111/j.1600-0412.2011.01230.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Bartolotta SA, Pacskowski MG, Hick A, Carballo MA. Micronuclei assay in exfoliated buccal cells from individuals exposed to arsenic in Argentina. ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2011; 61:337-343. [PMID: 20957353 DOI: 10.1007/s00244-010-9607-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2010] [Accepted: 09/13/2010] [Indexed: 05/30/2023]
Abstract
Drinking arsenic (As)-laden water for a long time affects a population's health and leads to chronic hydroarsenicism, which is associated with an increased incidence of different types of cancer. To determine the potential genotoxic risk associated with different degrees of environmental exposure to inorganic As by way of drinking water, micronuclei (MN) frequency in exfoliated buccal cells was evaluated in Argentina among rural populations of Santiago del Estero and urban populations of Buenos Aires. The exposed group in Santiago del Estero (La Firmeza and Santos Lugares localities) showed a significant increase in MN frequency in epithelial cells compared with controls (Monte Quemado and Urutau localities) (p = 0.0005). With regard to the Buenos Aires groups, Navarro individuals (the exposed group) exhibited a significant difference compared with controls (Ciudad Autónoma de Buenos Aires) (p = 0.0002). Comparison of MN frequencies between Santiago del Estero and Buenos Aires individuals showed that genotoxic effects of As in drinking water exhibit variation between rural and urban groups, probably due to individual susceptibility being an important incidence factor. The results clearly show that MN assay in buccal mucosa cells is an ideal methodology with which to measure potential genetic risk related to environmental As exposure in humans.
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Affiliation(s)
- Susana Alicia Bartolotta
- Citogenética Humana y Genética Toxicológica, Instituto de Fisiopatología y Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 CABA, Buenos Aires, Argentina
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Samanta S, Dey P, Gupta N, Mouleeswaran KS, Nijhawan R. Micronucleus in atypical squamous cell of undetermined significance. Diagn Cytopathol 2011; 39:242-4. [DOI: 10.1002/dc.21368] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Khan MI, Ahmad I, Mahdi AA, Akhtar MJ, Islam N, Ashquin M, Venkatesh T. Elevated blood lead levels and cytogenetic markers in buccal epithelial cells of painters in India: genotoxicity in painters exposed to lead containing paints. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2010; 17:1347-1354. [PMID: 20300868 DOI: 10.1007/s11356-010-0319-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2009] [Accepted: 02/21/2010] [Indexed: 05/29/2023]
Abstract
BACKGROUND, AIM, AND SCOPE Lead, a major contaminant, is highly used in paint manufacturing due to its anticorrosive properties. Recent reports indicated high lead content among Indian paints used for commercial purposes. Painters are continuously exposed to these lead containing paints during painting of both commercial as well as residential buildings. Lead is well-known for its genotoxicty in occupational workers; however, in Indian painters the genotoxic effects of lead have not been reported to date. Therefore we aimed to study the genotoxic end points in painters due to their long-term exposure to these high lead-containing Indian paints. MATERIALS AND METHODS Study group selection was made after a questionnaire administration, which included questions about lifestyle and medical history to exclude exposure to the other potential sources of genotoxics. Blood and buccal cell samples were obtained from 30 male painters and from a similar number of age-matched controls of same location with no occupational exposure to lead. Blood lead levels (Pb-B) were measured in painters and controls. Micronucleus (MN) frequencies and nuclear changes, i.e., karyorrhexis, karyolysis, broken egg, and binucleated, were investigated in buccal epithelial cells. RESULTS Painters had significantly (P < 0.01) greater lead levels in blood than the control group. MN frequencies and nuclear changes in buccal epithelial cells were also significantly (P < 0.01) elevated in painters as compared with control subjects. Regression analysis also revealed significant (P < 0.01) association of Pb-B with all the genotoxic endpoints in painters. Cytogenetic damage was significantly associated with Pb-B as no other co-founding factors (smoking, alcohols) showed significant difference between both groups. DISCUSSION Lead is widely used in paints which may serve as potential source of exposure among painters due to their long-term engagement with paints. Our results clearly demonstrated genotoxicity among the exposed population as evident from increase micronucleus frequencies, frequent nuclear changes, and apoptosis. Many studies had previously related nuclear change events in buccal epithelial cells with the progression of different carcinomas. Furthermore in-depth investigations with larger sample size are needed to provide evidence to this effect. CONCLUSIONS Here, we report cytogenetic toxicity to the exposed population by the high lead containing paints from India for the first time. Frequent, high and unregulated use of lead in paints may cause genetic mutation and may accelerate cytogenetic damage which may further lead to different carcinomas in painters. These findings need to be considered and necessary steps should be taken to protect the occupational workers engaged with these high lead-containing paints. RECOMMENDATIONS The use of lead in paints is completely unregulated in India and routine surveillance of paints for lead content is still lacking. These paints are readily available in markets and are also used in other products (jewelry, miniblinds) which could be exported to other countries including United States and Europe. Serious consideration should be given to the inclusion of regulations and bans on the use of lead in paints. Moreover, attention should also be paid towards the use of various protective measures (face-masks, hand gloves, and separate clothes) by the workers as safe work practices during working periods.
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Affiliation(s)
- Mohd Imran Khan
- National Referral Centre for Lead Poisoning in India, U.P., Department of Biochemistry, C.S.M. Medical University, Lucknow, India.
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Kaur J, Dey P. Micronucleus to distinguish adenocarcinoma from reactive mesothelial cell in effusion fluid. Diagn Cytopathol 2010; 38:177-9. [PMID: 19693939 DOI: 10.1002/dc.21168] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
To evaluate the role of the scoring of micronucleated cell (MNC) to distinguish reactive mesothelial cells from adenocarcinoma cells in effusion fluid. A total of 20 cases of unequivocal metastatic adenocarcinoma and 15 controls with reactive mesothelial cell proliferation in ascetic fluid were selected for scoring of the MNC. The numbers of cells having micronuclei were counted per 1000 of the well-preserved cells in May Grunwald Giemsa stained slides in each case. The mean number of MNC in metastatic adenocarcinoma and reactive mesothelial cells were 21 + 6.53 and 2.93 + 2.63, respectively, per 1000 cells. Micronuclei frequency was significantly increased in adenocarcinoma patients compared with controls (Student's t-test, P < 0.001). The scoring of MNC can be used as an additional biomarker and to discriminate between benign reactive mesothelial cells versus metastatic adenocarcinoma in effusion fluids in difficult situation.
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Affiliation(s)
- Jasleen Kaur
- Department of Cytology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Campos LMFDR, Dias FDL, Antunes LMG, Murta EFC. Prevalence of micronuclei in exfoliated uterine cervical cells from patients with risk factors for cervical cancer. SAO PAULO MED J 2008; 126:323-8. [PMID: 19274319 PMCID: PMC11025997 DOI: 10.1590/s1516-31802008000600006] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2007] [Revised: 11/21/2007] [Accepted: 11/04/2008] [Indexed: 11/22/2022] Open
Abstract
CONTEXT AND OBJECTIVE Pap smears are the most common and inexpensive screening method for cervical cancer. We analyzed micronucleus prevalence in exfoliated cervical mucosa cells, to investigate associations between increased numbers of micronuclei and risk factors for cervical cancer. DESIGN AND SETTING Analytical cross-sectional study, at Instituto de Pesquisa em Oncologia (IPON). METHODS Exfoliated cervical cells were obtained from 101 patients between September 2004 and November 2005. Patients' ages, habits (passive or active smoking, alcoholism and numbers of sexual partners), age at first sexual intercourse, contraceptive methods used, histories of sexually transmitted diseases, use of hormone replacement therapy, numbers of pregnancies and abortions, inflammatory cytology and cervical intraepithelial neoplasia (CIN) were obtained. Cells were collected using Ayre spatulas, transferred to vials containing 0.9% saline solution for micronucleus tests and analyzed at 1000x magnification. The number of micronuclei in 1,000 epithelial cells per patient sample was counted. RESULTS Comparisons between groups with active (7.9 +/- 7.8) and passive (7.2 +/- 10.6) smoking versus no smoking (3.7 +/- 5.1); with/without alcoholism (7.8 +/- 1.4 and 6.9 +/- 10.1); with/without inflammatory cytology (10.7 +/- 10.5 and 1.3 +/- 1.7); and with CIN I, II and III and no CIN (respectively 4.3 +/- 4.3, 10.6 +/- 5.3, 22.7 +/- 11.9 and 1.3 +/- 1.4) found elevated micronucleus prevalence (P < 0.05). CONCLUSIONS We concluded that the prevalence of micronuclei in exfoliated uterine cervical cells was greater in patients with one or more risk factors for uterine cervical cancer than in patients without risk factors.
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Affiliation(s)
| | | | | | - Eddie Fernando Candido Murta
- Eddie Fernando Candido Murta Instituto de Pesquisa em Oncologia (IPON), Disciplina de Ginecologia e Obstetrícia, Universidade Federal do Triângulo Mineiro (UFTM) Av. Getúlio Guarita, s/nº Uberaba (MG) — Brasil — CEP 38025-440 Tel. (+55 34) 3318-5326 Fax. (+55 34) 3318-5342 E-mail: E-mail:
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Ghosh P, Basu A, Singh KK, Giri AK. Evaluation of cell types for assessment of cytogenetic damage in arsenic exposed population. Mol Cancer 2008; 7:45. [PMID: 18505595 PMCID: PMC2430711 DOI: 10.1186/1476-4598-7-45] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2008] [Accepted: 05/28/2008] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Cytogenetic biomarkers are essential for assessing environmental exposure, and reflect adverse human health effects such as cellular damage. Arsenic is a potential clastogen and aneugen. In general, the majority of the studies on clastogenic effects of arsenic are based on frequency of micronuclei (MN) study in peripheral lymphocytes, urothelial and oral epithelial cells. To find out the most suitable cell type, here, we compared cytogenetic damage through MN assay in (a) various populations exposed to arsenic through drinking water retrieved from literature review, as also (b) arsenic-induced Bowen's patients from our own survey. RESULTS For literature review, we have searched the Pubmed database for English language journal articles using the following keywords: "arsenic", "micronuclei", "drinking water", and "human" in various combinations. We have selected 13 studies consistent with our inclusion criteria that measured micronuclei in either one or more of the above-mentioned three cell types, in human samples. Compared to urothelial and buccal mucosa cells, the median effect sizes measured by the difference between people with exposed and unexposed, lymphocyte based MN counts were found to be stronger. This general pattern pooled from 10 studies was consistent with our own set of three earlier studies. MN counts were also found to be stronger for lymphocytes even in arsenic-induced Bowen's patients (cases) compared to control individuals having arsenic-induced non-cancerous skin lesions. CONCLUSION Overall, it can be concluded that MN in lymphocytes may be superior to other epithelial cells for studying arsenic-induced cytogenetic damage.
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Affiliation(s)
- Pritha Ghosh
- Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata-700 032, India.
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Ergene S, Celik A, Cavaş T, Kaya F. Genotoxic biomonitoring study of population residing in pesticide contaminated regions in Göksu Delta: micronucleus, chromosomal aberrations and sister chromatid exchanges. ENVIRONMENT INTERNATIONAL 2007; 33:877-85. [PMID: 17493680 DOI: 10.1016/j.envint.2007.04.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2006] [Revised: 04/05/2007] [Accepted: 04/10/2007] [Indexed: 05/15/2023]
Abstract
Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless, exposure to pesticides represents a potential risk to humans. This paper describes a study of possible genetic damage in the people living in regions contaminated with complex mixture of pesticides in Göksu Delta. In this study, used methods were chromosomal aberration (CA), sister chromatid exchange analysis (SCE) in the peripheral blood lymphocytes, and micronucleus (MN) assay in the buccal epithelial cells. In the present investigation, 32 affected subjects consist of 16 smoking and 16 non-smokings and an equal number of control subjects were assessed for genome damage. Micronucleus (MN), Broken egg (BE), Karyorrhexis (KR), Karyolysis (KL) and Binucleus (BN) frequencies were higher in affected subjects than in controls. Smoking had a statistically significant effect on the Micronucleus, Karyorrhexis and Binucleus frequencies for both the control and the exposed group. Also smoking and exposure affected the frequency of sister chromatid exchange and chromosomal aberrations compared with control groups.
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Affiliation(s)
- Serap Ergene
- Department of Biology, Faculty of Science and Letters, Mersin University, Mersin, Turkey
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Nersesyan AK. Possible role of the micronucleus assay in diagnostics and secondary prevention of cervix cancer: A minireview. CYTOL GENET+ 2007. [DOI: 10.3103/s0095452707050106] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Korkmaz M, Uzgören E, Bakirdere S, Aydin F, Ataman OY. Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells. ENVIRONMENTAL TOXICOLOGY 2007; 22:17-25. [PMID: 17295277 DOI: 10.1002/tox.20229] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Recent evidence indicates that boron and borates may have anticarcinogenic properties. In this study, we have investigated the incidence of adverse cytological findings in cervical smears and the micronucleus (MN) frequency in women living in boron-rich and boron-poor regions. Cervical smears were prepared from 1059 women with low socioeconomic status; 472 of the women lived in relatively boron-rich rural areas, while 587 lived in relatively boron-poor regions. The average and standard deviation values for the age of the women screened with the cervical Pap smear test were 41.55 +/- 8.38. The mean dietary intake of boron was 8.41 mg/day for women from the boron-rich regions, and 1.26 mg/day for women living in the boron-poor regions (P < 0.0001). Women from the boron-rich regions had no cytopathological indications of cervical cancer, while there were cytopathological findings for 15 women from the boron-poor areas (chi(2) = 10.473, P < 0.05). Sixty women, 30 from each region, were chosen for evaluating MN frequencies in exfoliated buccal cells. MN frequencies for women from the boron-rich and boron-poor regions were not significantly different (t = -0.294, P > 0.05). Also, there were no significant correlations between age and MN frequency for women from both the boron-rich (r = 0.133, P = 0.48, P > 0.05) and boron-poor (r = -0.033, P = 0.861, P > 0.05) regions. The results suggest that ingestion of boron in the drinking water decreases the incidence of cervical cancer-related histopathological findings. There was no correlation between the pathological findings from the cervical smears and buccal cell MN frequency suggesting that the two study populations were exposed equally to gentotoxic agents. Nonetheless, cervical cancer-related histopathological findings should be validated by other researchers.
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Affiliation(s)
- Mehmet Korkmaz
- Department of Medical Biology, Faculty of Medicine, Yüzüncüyil University, 65200 Van, Turkey.
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Celik A, Kanik A. Genotoxicity of occupational exposure to wood dust: Micronucleus frequency and nuclear changes in exfoliated buccal mucosa cells. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2006; 47:693-8. [PMID: 17078100 DOI: 10.1002/em.20257] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
Occupational exposure to wood dust is associated with the occurrence of nasal cancer. In this study, we investigated micronuclei and nuclear changes (NCs: binucleates, karyorrhexis, karyolysis, and the "broken egg" effect) in exfoliated buccal cells of 20 workers exposed to wood dust and 20 age- and sex-matched controls. Micronucleus frequency and the frequency of each of the NCs were significantly higher for wood workers than controls (P < 0.01). Cigarette smoking was associated with increased frequencies of micronuclei and NCs in the buccal mucosa epithelium cells of both the control and exposed groups. Our findings indicate that buccal cells of wood workers display increased levels of genotoxicity and toxicity, and that these biomarker responses may be related to the increased cancer risk among wood workers.
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Affiliation(s)
- Ayla Celik
- Department of Biology, Faculty of Science and Letters, Mersin University, Mersin, Turkey.
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Decordier I, Kirsch-Volders M. The in vitro micronucleus test: From past to future. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2006; 607:2-4. [PMID: 16725370 DOI: 10.1016/j.mrgentox.2006.04.008] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Ornelas-Aguirre JM, Gómez-Meda BC, Zamora-Perez AL, Ramos-Ibarra ML, Batista-González CM, Zúñiga-González GM. Micronucleus induction by metronidazole in rat vaginal mucosa. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2006; 47:352-6. [PMID: 16628750 DOI: 10.1002/em.20214] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Metronidazole (MTZ) is used for the treatment of many infectious diseases, including vaginal infections. While data indicate that MTZ is mutagenic and induces micronuclei in rodents, there is no information on the genotoxicity of MTZ in epithelial vaginal cells or cervical cells. In the present study, we have instilled MTZ into the vagina of rats and evaluated the micronucleus (MN) frequency in proestrus rat vaginal mucosal cells. The first identified proestrus before treatment was used to establish basal proestrus micronucleated cell (PMNC) frequencies. Rats then were assigned to one of five groups: a negative control, three MTZ treatment groups (30, 50, or 100 mg/kg MTZ), and a positive control treated with 2.5 mg of 5-fluorouracil (5-Fu) per rat. Following treatment for five consecutive days, vaginal cell samples were taken daily until three cycles of estrus were completed. Smears prepared from the samples were evaluated for micronuclei in proestrus cells. No differences were found between the PMNC frequencies of the negative control and the 30 and 50 mg/kg MTZ groups. The group treated with 100 mg/kg MTZ, however, had significantly elevated PMNC frequencies in the first and second proestrus samples, while 5-Fu treatment produced significant increases in PMNC frequency in the second and third proestrus. These results indicate that topical administration of relatively high concentrations of MTZ is genotoxic in rat vaginal mucosa cells.
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Affiliation(s)
- José Manuel Ornelas-Aguirre
- Unidad de Investigación en Ciencias Médicas, Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, México
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Olaharski AJ, Sotelo R, Solorza-Luna G, Gonsebatt ME, Guzman P, Mohar A, Eastmond DA. Tetraploidy and chromosomal instability are early events during cervical carcinogenesis. Carcinogenesis 2005; 27:337-43. [PMID: 16123119 DOI: 10.1093/carcin/bgi218] [Citation(s) in RCA: 178] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Chromosomal instability as manifested by increases in aneuploidy and structural chromosome aberrations is believed to play a critical role in the intermediate to late stages in the development of cervical malignancies. The current study was designed to determine the role of tetraploidy in the formation of aneuploidy and ascertain the occurrence of these alterations during the earlier stages of cervical carcinogenesis. Cervical cell samples, with diagnoses ranging from Normal to high-grade lesions, (HSIL) were obtained from 143 women and were evaluated for chromosomal alterations using dual-probe fluorescence in situ hybridization. Cervical cells from a subset of the group were also evaluated for chromosomal instability in the form of micronuclei. The frequencies of cells exhibiting either tetrasomy or aneusomy for Chromosomes 3 and 17 increased significantly with disease progression and displayed distinctive patterns where aneusomy was rarely present in the absence of tetrasomy. The frequencies of micronuclei that formed through either chromosomal loss or breakage increased significantly in both the low-grade and high-grade diagnostic categories and were highly correlated with both the number of tetrasomic and aneusomic cervical cells. In addition, a unique chromosomal alteration involving a significant non-random loss of Chromosome 17 specific to near-tetraploid aneusomic cells (trisomy 17 and tetrasomy 3) was observed. We conclude that tetraploidy and chromosomal instability are related events occurring during the early stages of cervical carcinogenesis that predispose cervical cells to the formation of aneuploidy frequently involving the loss of Chromosome 17.
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Affiliation(s)
- Andrew J Olaharski
- Environmental Toxicology Graduate Program, Department of Cell Biology and Neuroscience, 5429 Boyce Hall, University of California, Riverside, CA-92521, USA
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Herrera LA, Benítez-Bribiesca L, Mohar A, Ostrosky-Wegman P. Role of infectious diseases in human carcinogenesis. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2005; 45:284-303. [PMID: 15744742 DOI: 10.1002/em.20122] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The burden of human infectious diseases remains a public health problem worldwide. At least 2 billion people are affected by viral infections, and a similar number by bacteria or helminths. The long-term effects of these maladies have raised particular concern since some infectious agents have been associated with chronic human diseases, especially cancer. It is estimated that 13-20% of the world cancer cases are associated with some virus, bacteria, or helminth, e.g., human papillomavirus, Helicobacter pylori, and Schistosoma haematobium that cause cervical, stomach, and urinary bladder cancer, respectively. Certain associations between infection and malignancy are strong and irrefutable; others are still speculative. This article reviews the infectious agents that have been associated with cancer and current knowledge about the mechanisms underlying these associations.
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Affiliation(s)
- Luis A Herrera
- Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Instituto Nacional de Cancerología, Mexico City, México
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Basu A, Ghosh P, Das JK, Banerjee A, Ray K, Giri AK. Micronuclei as Biomarkers of Carcinogen Exposure in Populations Exposed to Arsenic Through Drinking Water in West Bengal, India: A Comparative Study in Three Cell Types. Cancer Epidemiol Biomarkers Prev 2004. [DOI: 10.1158/1055-9965.820.13.5] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Abstract
Contamination of groundwater by arsenic, a paradoxical human carcinogen, has become a cause of global public health concern. In West Bengal, India, the groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various adverse health effects including cancer have been reported from these districts and are associated with prolonged arsenic exposure. A cross-sectional biomarker study was conducted to evaluate and compare the frequencies of micronuclei in peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the inhabitants of North 24 Parganas, one of the arsenic-affected districts. The three cell types were collected from 163 residents exposed to high levels of arsenic in drinking water (214.7213 ± 9.0273 μg/l) and from 154 unexposed subjects residing in the unaffected East Midnapur district with very little or no exposure to arsenic through drinking water (9.2017 ± 0.3157 μg/l). Our analysis revealed that micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63-fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in micronuclei frequencies significant at P < 0.01). The results indicate that chronic ingestion of arsenic in drinking water by the exposed subjects is linked to the enhanced incidence of micronuclei in all the three cell types, slightly higher level of micronuclei being observed in lymphocytes compared with oral mucosa and urothelial cells.
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Affiliation(s)
- Anamika Basu
- 1Division of Human Genetics and Genomics, Indian Institute of Chemical Biology, Calcutta, India and
| | - Pritha Ghosh
- 1Division of Human Genetics and Genomics, Indian Institute of Chemical Biology, Calcutta, India and
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- 2Department of Dermatology, West Bank Hospital, Howrah, India
| | - Apurba Banerjee
- 1Division of Human Genetics and Genomics, Indian Institute of Chemical Biology, Calcutta, India and
| | - Kunal Ray
- 1Division of Human Genetics and Genomics, Indian Institute of Chemical Biology, Calcutta, India and
| | - Ashok K. Giri
- 1Division of Human Genetics and Genomics, Indian Institute of Chemical Biology, Calcutta, India and
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