• Calf thymus DNA
• Genotoxicity
• Groove binding interaction
• Molecular docking
• Piperlongumine
• Spectroscopy

• Circular Dichroism
• DNA/chemistry
• DNA, B-Form
• Dioxolanes
• Molecular Docking Simulation
• Nucleic Acid Conformation
• Spectrometry, Fluorescence
• Spectrophotometry, Ultraviolet
• Thermodynamics

• GMA exposure
• Glycidyl methacrylate (CAS no. 106-91-2)
• carcinogenicity
• genotoxicity
• occupational health

• Ceramic
• Clinical significance
• Composite
• Review
• Wear methods

• Apoptosis
• DNA damage
• Diethylene glycol dimethacrylate
• Ethylene glycol dimethacrylate
• Human gingival fibroblasts
• Reactive oxygen species

• 53BP1
• Chromatin
• DNA damage
• NAC
• γ-H2AX

• Composites
• Cytotoxicity
• Degree of conversion
• Flexural strength
• Own brand label
• Residual monomers

• 53BP1
• Chromatin
• DNA damage
• DNA double-strand breaks
• Dental composites
• Gingiva fibroblasts
• Monomers
• Nuclear morphology
• γ-H2AX

• 3T3 Cells
• Acid Etching, Dental/methods
• Adhesives
• Animals
• Biocompatible Materials/chemistry
• Cell Survival
• Dental Bonding
• Dentin/chemistry
• Dentin-Bonding Agents/chemistry
• Materials Testing
• Methacrylates/chemistry
• Mice
• Molecular Weight
• Resin Cements/chemistry
• Spectroscopy, Fourier Transform Infrared
• Stress, Mechanical

• Ethanol
• Neurotoxicity
• PC12 cells
• Pb

AIM: To evaluate the direct and indirect biocompatibility of Filtek Silorane on human gingival fibroblastic cells.

METHODS: Sixty-three standardized cylindrical specimens (8 mm diameter and 2 mm thickness) of restorative material were prepared using a light emitting diode-curing unit. The sample were built up in one increment and divided in 2 groups. In the first group, 21 samples (unpolished samples) were left without a specific polishing procedure; in the second one, 42 samples (polished samples) were polished with 4 different grains of discs. Fibroblast cultures, obtained from gingiva of 2 subjects without systemic and oral disease, were used to assess the direct and indirect biocompatibility. Cells cultured for 48 h in normal culture medium were used as a control.

RESULTS: The scanning electron microscope observations of fibroblasts cultured on the silorane samples, either polished or unpolished, confirmed the good biocompatibility of the material, favouring the cellular spreading. 3-dimethylthiazol-2, 5-diphenyltetrazolium bromide tests showed a significant reduction (P < 0.01) of gingival fibroblasts viability cultured both in polished samples (90.05% ± 19.00%) and unpolished samples (78.15% ± 11.00%) compared with the control. Cells growth in medium conditioned with the samples for 1 wk showed a significant viability reduction (P < 0.01) compared to the control. A reduction of cell viability was observed even in the groups containing the material for 3 wk (polished: 89.45% ± 10.00%; unpolished: 65.97% ± 10.00%), even if the cytotoxicity was reduced after this long time exposure.

CONCLUSION: Although the poor chromatic availability of this material remains a big limit that restricts its use to posterior sectors, the silorane-based material can be considered an option to perform restorations when aesthetic demands are not the priority, such as the class II restorations

• Silorane
• Cytotoxicity
• Resin composite
• Fibroblasts

Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. This bacterium may induce cancer transformation and change the susceptibility of gastric mucosa cells to various exogenous dietary irritants. The aim of the study was to evaluate the influence of H. pylori infection on the reaction of the stomach cells to a genotoxic effect of heterocyclic amines (HCAs). These well-known mutagens are formed during cooking of protein-rich foods, primarily meat. Taking into account that persons consuming a mixed-western diet are exposed to these compound nearly an entire lifetime and more than half of human population is infected with H. pylori, it is important to assess the combined effect of H. pylori infection and HCAs in the context of DNA damage in gastric mucosa cells, which is a prerequisite to cancer transformation. We employed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) because these substances are present in a great amount in cooked and fried meat. Using alkaline comet assay, we showed that the extent of the DNA damage induced by HCAs was significantly higher in H. pylori infected gastric mucosa cells than in non-infected counterparts. We did not observed any difference in the efficiency of repair of DNA lesions induced by HCAs in both type of cells. Vitamin C reduced the genotoxic effects of HCAs in H. pylori infected and non-infected gastric mucosa cells. Melatonin more effectively decreased DNA damage caused by HCAs in H. pylori infected gastric mucosa cells as compared with control. Our results suggest that H. pylori infection may influence the susceptibility of gastric mucosa cells to HCAs and dietary antioxidative substances, including vitamin C and melatonin may inhibit the genotoxic effects of HCAs on gastric mucosa cells and may reduce the risk of carcinogenesis caused by food borne mutagens and H. pylori infection.

• Adult
• Ascorbic Acid/pharmacology
• Breath Tests
• Carbon Isotopes/metabolism
• Comet Assay
• DNA Damage/drug effects
• DNA Damage/genetics
• Female
• Gastric Mucosa/drug effects
• Gastric Mucosa/microbiology
• Helicobacter Infections/metabolism
• Helicobacter pylori
• Humans
• Imidazoles/toxicity
• Male
• Melatonin/pharmacology
• Middle Aged
• Poland
• Quinoxalines/toxicity
• Statistics, Nonparametric

Methacrylate monomers used in dentistry have been shown to induce DNA double strand breaks (DSBs), one of the most serious DNA damage. In the present work we show that a model dental adhesive consisting of 45% 2-hydroxyethyl methacrylate (HEMA) and 55% bisphenol A-diglycidyl dimethacrylate (Bis-GMA) at concentrations up to 0.25 mM Bis-GMA induced oxidative DNA in cultured primary human gingival fibroblasts (HGFs) as evaluated by the comet assay and probed with human 8-hydroxyguanine DNA-glycosylase 1. HEMA/Bis-GMA induced DSBs in HGFs as assessed by the neutral comet assay and phosphorylation of the H2AX histone and sodium ascorbate or melatonin (5-methoxy-N-acetyltryptamine) both at 50 μM reduced the DSBs, they also inhibited apoptosis induced by HEMA/Bis-GMA. The adhesive slowed the kinetics of the repair of DNA damage induced by hydrogen peroxide in HGFs, while sodium ascorbate or melatonin improved the efficacy of H₂O₂-induced damage in the presence of the methacrylates. The adhesive induced a rise in the G2/M cell population, accompanied by a reduction in the S cell population and an increase in G0/G1 cell population. Sodium ascorbate or melatonin elevated the S population and reduced the G2/M population. In conclusion, HEMA/Bis-GMA induce DSBs through, at least in part, oxidative mechanisms, and these compounds may interfere with DSBs repair. Vitamin C or melatonin may reduce the detrimental effects induced by methacrylates applied in dentistry.

Monomers of methacrylates used in restorative dentistry have been recently reported to induce DNA double-strand breaks (DSBs) in human gingival fibroblasts (HGFs) in vitro. Because such monomers may penetrate the pulp and oral cavity due to the incompleteness of polymerization and polymer degradation, they may induce a similar effect in vivo. DSBs are the most serious type of DNA damage and if misrepaired or not repaired may lead to mutation, cancer transformation and cell death. Therefore, the protection against DSBs induced by methacrylate monomers released from dental restorations is imperative.

We examined the protective action of chitosan oligosaccharide lactate (ChOL) against cytotoxic and genotoxic effects induced by monomers of the model adhesive consisting of 55% bisphenol A-diglycidyl dimethacrylate (Bis-GMA) and 45% 2-hydroxyethyl methacrylate (HEMA). We evaluated the extent of DSBs by the neutral comet assay and the phosphorylation of the H2AX histone test.

ChOL increased the viability of HGFs exposed to Bis-GMA/HEMA as assessed by flow cytometry. ChOL decreased the extent of DSBs induced by Bis-GMA/HEMA as evaluated by neutral comet assay and phosphorylation of the H2AX histone. ChOL did not change mechanical properties of the model adhesive, as checked by the shear bond test. Scanning electron microscopy revealed a better sealing of the dentinal microtubules in the presence of ChOL, which may protect pulp cells against the harmful action of the monomers.

ChOL can be considered as an additive to methacrylate-based dental materials to prevent DSBs induction, but further studies are needed on its formulation with the methacrylates.

• Animals
• Antioxidants/therapeutic use
• Cytotoxins/adverse effects
• DNA Damage/drug effects
• Dental Materials/adverse effects
• Melatonin/therapeutic use
• Methacrylates/adverse effects

HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action.

• Apoptosis/drug effects
• Cell Line
• Comet Assay
• DNA Breaks, Double-Stranded/drug effects
• Dental Materials/metabolism
• Dental Materials/toxicity
• Fibroblasts/drug effects
• Flow Cytometry
• Gingiva/cytology
• Gingiva/drug effects
• Humans
• Methacrylates/chemistry
• Methacrylates/metabolism
• Methacrylates/toxicity
• Molecular Structure
• Mutagens/chemistry
• Mutagens/metabolism
• Mutagens/toxicity
• Statistics, Nonparametric

• Aluminum/toxicity
• Animals
• Carps
• Cytotoxins/toxicity
• Dose-Response Relationship, Drug
• Lymphocytes/drug effects
• Mutagens/toxicity
• Water Pollutants, Chemical/toxicity

Dental composite materials contain polymers of methacrylates, which, due to mechanical abrasion and enzymatic action of saliva, may release their monomers into oral cavity and the pulp. Moreover, polymerization is always incomplete and leaves usually considerable fraction of free monomers. Mechanisms of the genotoxicity of methacrylate monomers have been rarely explored. As the polymerization of a monomer is catalyzed by a co-monomer, their combined action should be considered. In the present work, we investigated cytotoxic and genotoxic effects of urethane dimethacrylate (UDMA), often used as a monomer, at 1 mM, and triethylene glycol dimethacrylate (TEGDMA), a typical co-monomer, at 5 mM singly and in combination. Experiments were conducted on Chinese hamster ovary cells. Cell viability, apoptosis and cell cycle were assessed by flow cytometry, whereas DNA damage was evaluated by plasmid conformation test and comet assay. Both compounds decreased the viability of the cells, but did not induce strand breaks in an isolated plasmid DNA. However, both substances, either singly or in combination, damaged DNA in CHO cells as evaluated by comet assay. Both compounds induced apoptosis, but a combined action of them led to a decrease in the number of apoptotic cells. The combined action of UDMA and TEGDMA in the disturbance of cell cycle was lesser compared to the action of each compound individually. Individually, though UDMA and TEGDMA may induce cytotoxic and genotoxic, however, a combination of both does not produce a significant increase in these effects.

• Carcinogens/toxicity
• Cell Line
• Humans
• Metal Nanoparticles
• Microscopy, Electron, Transmission
• Mutagens/toxicity
• Reactive Oxygen Species/metabolism
• Spectroscopy, Fourier Transform Infrared
• Spectrum Analysis/methods
• Surface Properties
• X-Rays
• Zinc Oxide/toxicity

Bisphenol A-glycidyl methacrylate (BisGMA) is monomer of dental filling composites, which can be released from these materials and cause adverse biologic effects in human cells. In the present work, we investigated genotoxic effect of BisGMA on human lymphocytes and human acute lymphoblastic leukemia cell line (CCRF-CEM) cells. Our results indicate that BisGMA is genotoxic for human lymphocytes. The compound induced DNA damage evaluated by the alkaline, neutral, and pH 12.1 version of the comet assay. This damage included oxidative modifications of the DNA bases, as checked by DNA repair enzymes EndoIII and Fpg, alkali-labile sites and DNA double-strand breaks. BisGMA induced DNA-strand breaks in the isolated plasmid. Lymphocytes incubated with BisGMA at 1 mM were able to remove about 50% of DNA damage during 120-min repair incubation. The monomer at 1 mM evoked a delay of the cell cycle in the S phase in CCRF-CEM cells. The experiment with spin trap—DMPO demonstrated that BisGMA induced reactive oxygen species, which were able to damage DNA. BisGMA is able to induce a broad spectrum of DNA damage including severe DNA double-strand breaks, which can be responsible for a delay of the cell cycle in the S phase.

• Bisphenol A-Glycidyl Methacrylate/toxicity
• Cell Cycle/drug effects
• Cell Line, Tumor
• Comet Assay
• DNA Breaks, Double-Stranded/drug effects
• DNA Repair
• DNA Repair Enzymes/metabolism
• Humans
• Lymphocytes/cytology
• Lymphocytes/drug effects
• Plasmids
• Reactive Oxygen Species/metabolism
• S Phase/drug effects