External Versus Internal Metabolic Activation of Polycyclic Aromatic Compounds in Mutagenicity Tests: A Comparison Using Heterologous Expression Systems

Abstract

Abstract Benzo[a]pyrene-trans-7,8-dihydrodiol was virtually non-mutagenic to Chinese hamster V79p cells, but was strongly mutagenic to a V79-derived cell line expressing cytochrome P450 1A1, when the cells were exposed separately. In mixed cultures of these two cell types, it showed about 50 % of the mutagenic activity in V79p cells, compared to that observed in the enzyme-proficient cell line, indicating an efficient intercellular transfer of the active metabolite. The benzylic alcohols 1-hydroxymethylpyrene and 6-hydroxymethylbenzo[a]-pyrene were weakly mutagenic to Salmonella typhimurium TA1538 in the absence of a metabolic activation system, but were potent mutagens to a TA1538-derived strain expressing human hydroxysteroid sulfotransferase. 1-Hydroxymethylpyrene also showed strong mutagenicity to TA 1538 in the presence of chloride anions and cofactor-supplemented cytosol of the genetically engineered strain. This was not the case with 6-hydroxymethylbenzo[a]pyrene. It is concluded that some reactive...