Brief Article
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World J Gastroenterol. Aug 28, 2013; 19(32): 5295-5301
Published online Aug 28, 2013. doi: 10.3748/wjg.v19.i32.5295
Investigation of genome instability in patients with non-alcoholic steatohepatitis
Hatice Karaman, Ahmet Karaman, Hamiyet Donmez-Altuntas, Nazmiye Bitgen, Zuhal Hamurcu, Arzu Oguz, Cigdem Karakukcu
Hatice Karaman, Department of Pathology, Kayseri Education and Research Hospital, 38030 Kayseri, Turkey
Ahmet Karaman, Department of Gastroenterology, Kayseri Education and Research Hospital, 38030 Kayseri, Turkey
Hamiyet Donmez-Altuntas, Nazmiye Bitgen, Zuhal Hamurcu, Department of Medical Biology, Medical School, Erciyes University, 38030 Kayseri, Turkey
Arzu Oguz, Department of Medical Oncology, Kayseri Education and Research Hospital, 38030 Kayseri, Turkey
Cigdem Karakukcu, Department of Clinical Biochemistry, Kayseri Education and Research Hospital, 38030 Kayseri, Turkey
Author contributions: Karaman H and Karaman A designed the study, collected the data and wrote the manuscript; Donmez-Altuntas H, Bitgen N and Hamurcu Z evaluated the micronucleus assays; and Oguz A and Karakukcu C edited the manuscript.
Correspondence to: Hatice Karaman, MD, Department of Pathology, Kayseri Education and Research Hospital, Alpaslan Mah. Emrah Cad. Beyoğlu Apt. 21/3 Melikgazi, 38030 Kayseri, Turkey. htckaraman@yahoo.com
Telephone: +90-505-2593155 Fax: +90-352-3368857
Received: March 7, 2013
Revised: May 17, 2013
Accepted: June 1, 2013
Published online: August 28, 2013
Abstract

AIM: To evaluate the occurrence of micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with non-alcoholic steatohepatitis (NASH).

METHODS: The study was performed in 25 (9 females, 16 males) patients newly diagnosed with NASH, and 25 healthy subjects of similar ages and genders were used as a control group. None of the controls was known to be receiving any drugs for medical or other reasons or using alcohol. Hepatosteatosis was further excluded by abdominal ultrasound imaging in the control group. The numbers of MN, NPBs and NBUDs scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. Statistical comparisons of the numbers of BN cells with MN, NPBs and NBUDs and ages between the patients with NASH and control subjects were performed.

RESULTS: The mean ages of the patients and the control group were 41.92 ± 13.33 and 41.80 ± 13.09 years (P > 0.05), respectively. The values of the mean body mass index (BMI), HOMA-IR, hemoglobin, creatinin, aspartate aminotransferase, alanine aminotransferase, triglyceride, high density lipoprotein, and low density lipoprotein were 31.19 ± 4.62 kg/m2vs 25.07 ± 4.14 kg/m2, 6.71 ± 4.68 vs 1.40 ± 0.53, 14.73 ± 1.49 g/dL vs 14.64 ± 1.30 g/dL, 0.74 ± 0.15 mg/dL vs 0.80 ± 0.13 mg/dL, 56.08 ± 29.11 U/L vs 16.88 ± 3.33 U/L, 92.2 ± 41.43 U/L vs 15.88 ± 5.88 U/L, 219.21 ± 141.68 mg/dL vs 102.56 ± 57.98 mg/dL, 16.37 ± 9.65 mg/dL vs 48.72 ± 15.31 mg/dL, and 136.75 ± 30.14 mg/dL vs 114.63 ± 34.13 mg/dL in the patients and control groups, respectively. The total numbers and frequencies of BN cells with MN, NPBs and NBUDs, which were scored using the CBMN cytome assay on PHA-stimulated lymphocytes, were evaluated in the patients with NASH and control group. We found significantly higher numbers of MN, NPBs and NBUDs in the BN cells of patients with NASH than in those of the control subjects (21.60 ± 9.32 vs 6.88 ± 3.91; 29.28 ± 13.31 vs 7.84 ± 3.96; 15.60 ± 5.55 vs 4.20 ± 1.63, respectively, P < 0.0001).

CONCLUSION: The increased numbers of MN, NPBs and NBUDs observed in the lymphocytes obtained from patients with NASH may reflect genomic instability.

Keywords: Non-alcoholic steatohepatitis, Micronucleus, Nucleoplasmic bridges, Nuclear buds

Core tip: We aimed to evaluate the micronucleus, nucleoplasmic bridges and nuclear buds in the mitogen-stimulated lymphocytes of patients with non-alcoholic steatohepatitis (NASH). Genomic instability may be a stage in the development of hepatic carcinogenesis. NASH is a major cause of so-called cryptogenic liver cirrhosis and can result in hepatocellular carcinoma (HCC). Our results support this suggestion; although none of the patients had liver cirrhosis in our study, there is high genomic instability in their mitogen-stimulated lymphocytes. Further prospective studies are needed to further clarify this topic, especially among patients with HCC, cirrhosis and NASH.