Mutagenicity of benzo[a]pyrene and dibenzopyrenes in the Salmonella typhimurium TM677 and the MCL-5 human cell forward mutation assays

Abstract

The mutagenicity of beno[ a]pyrene (B[ a]P), dibenzo[ ae]pyrene (DB[ ae]P), dibenzo[ ah]pyrene (DB[ ah]P), dibenzo[ ai]pyrene (DB[ ai]P) and dibenzo[ al]pyrene (DB[ ai]P was measured in quantitative forward mutation assays with bacteria ( Salmonella typhimuriu TM677) and a metabolically copettent cell line derived from human B-lymphoblastoid cells (MCL-5) that contained activity for five cytochrome P450s and microsomal epoxide hydrolase found in human liver. DB[ al]P and B[ a]P, both potent animal carcinogens, were the most mutagenic substances in both assays. DB[ al]P was nearly 50-fold more potent than B[ a]P in human cells. but only 60% more mutagenic in Salmonella. The carcinogenic isomer DB[ ah]P, though nonmutagenic in bacteria, was active in human cells. The following mutagenic potency series, expressed as the minimum detectable mutagen concentration (MDMC) in nmol/ml, was obtained with Salmonella in the presence of rat liver postmitochondrial supernatant (PMS): DB[ al]P(3.7), B[ a]P (5.8), DB ae]P (6.9), DB[ ai]P (14.9), DB[ ah]P (> 100). None of the compounds were mutagenic in the absence of PMS. In human MCL-5 cells the potency series was: DB[ al]P (3.1 × 10 −4), B[ a]P (1.5 × 10 −2), DB[ ae]P (2.5 × 10 −2), DB[ ah]P (0.5), DB[ ai]P (3.2). The human cell assay thus exhibited over a 10 000-fold range between the most mutagenic and least mutagenic compound, whereas in the bacterial assay there was only a corresponding four-fold difference if the nonmutagenic DB[ ah]P was excluded. The results were discussed in terms of their concordance with animal carcinogenicity studies.