Mutation in mammalian cells by stereoisomers of anti-benzo[a] pyrene-diolepoxide in relation to the extent and nature of the DNA reaction products.

Monolayer cultures of V79 cells were treated with tritium labelled (+) and (-) stereoisomers of anti-benzo[a]pyrene diolepoxide. Cell survival and induction of 8-azaguanine resistant mutants by the two stereoisomers were related to the extent of reaction with cellular DNA and to the nature of the reaction products. At equal extents of DNA reaction both isomers were equally cytotoxic but the (+) anti-isomer was considerably more mutagenic. This difference of mutagenicity could not be related to any particular product of DNA reaction or to differential excision repair by the V79 cells. It is proposed that mutagenicity in V79 cells, which correlates closely with reported carcinogenicity data in mice, is a consequence of reaction with DNA at the amino-group of guanine and that the difference found between the (+) and (-) stereoisomers results from differences in the spatial orientation of the benzo[a]pyrene residue at this site.