Suppressive effects of methyl methacrylate on the mutagenicity and DNA adduct formation induced by 1-nitropyrene and benzo[a]pyrene

Methyl methacrylate (MMA) is widely used as a cement in dentistry,orthopaedic surgery and ophthalmology. Studies based on short-termgenotoxicity tests have produced conflicting results in thelast two decades. In the present study, the effects of MMA onthe mutagenicity of 1-nitropyrene (1-NP) and benzo[a]pyrene(B[a]P) were evaluated with the Salmonella typhimurium TA98strain in the absence and presence of S9 mix. The direct-actingmutagenicity of 1-NP was markedly decreased by MMA in a dose-dependentmanner. However, a low inhibitory effect of MMA on the metabolic-actingmutagenicity of B[a]P was observed. MMA did not show mutagenicitywithin the concentrations of 4.7–37.6 µM eitherwith or without S9 mix. The inhibitory effect of MMA was notdue to its cytotoxicity because very low and/or no cytotoxicityof MMA to S.typhimurium TA98 was observed. To confirm the antimutagenicityof MMA against 1-NP and B[a]P, a ³²P-postlabelling method wasused to determine whether MMA modified DNA adduct formationproduced by both compounds in calf thymus DNA. MMA inhibitsthe formation of 1-NP- and B[a]P-DNA adducts in a dose-dependentmanner. The DNA adduct of 1-NP reduced by MMA was greater thanthat of B[a]P. Thus, we suggested that MMA was possibly actingas an inhibitor of chemical carcinogenesis. ¹To whom correspondence should be addressed