Dental methacrylates may exert genotoxic effects via the oxidative induction of DNA double strand breaks and the inhibition of their repair.
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 H(2)O(2)-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.
Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. jblasiak@biol.uni.lodz.pl
Janusz
J
Blasiak
Ewelina
E
Synowiec
Justyna
J
Tarnawska
Piotr
P
Czarny
Tomasz
T
Poplawski
Russel J
RJ
Reiter
D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D003188:Composite Resins / Q000633:toxicity; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000187:drug effects*; D003738:Dental Cements / Q000633:toxicity*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008550:Melatonin / Q000494:pharmacology; D008689:Methacrylates / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*
D003188:Composite Resins; D003738:Dental Cements; D008689:Methacrylates; D009153:Mutagens; D008550:Melatonin; D001205:Ascorbic Acid