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

Abstract

Methyl methacrylate (MMA) is widely used as a cement in dentistry, orthopaedic surgery and ophthalmology. Studies based on short-term genotoxicity tests have produced conflicting results in the last two decades. In the present study, the effects of MMA on the mutagenicity of 1-nitropyrene (1-NP) and benzo[a]pyrene (B[a]P) were evaluated with the Salmonella typhimurium TA98 strain in the absence and presence of S9 mix. The direct-acting mutagenicity of 1-NP was markedly decreased by MMA in a dose-dependent manner. However, a low inhibitory effect of MMA on the metabolic-acting mutagenicity of B[a]P was observed. MMA did not show mutagenicity within the concentrations of 4.7-37.6 microM either with or without S9 mix. The inhibitory effect of MMA was not due to its cytotoxicity because very low and/or no cytotoxicity of MMA to S. typhimurium TA98 was observed. To confirm the antimutagenicity of MMA against 1-NP and B[a]P, a 32P-postlabelling method was used to determine whether MMA modified DNA adduct formation produced by both compounds in calf thymus DNA. MMA inhibits the formation of 1-NP- and B[a]P-DNA adducts in a dose-dependent manner. The DNA adduct of 1-NP reduced by MMA was greater than that of B[a]P. Thus, we suggested that MMA was possibly acting as an inhibitor of chemical carcinogenesis.