Mutation at Separate Gene Loci in Salmonella typhimurium TA 100 Related to DMA Nucleotide Modification by Stereoisomeric Benzo(a)pyrene 7,8-Diol- 9,10-epoxides1

Suspensions of Salmonella typhimurium TA100 or TA1535 cells were exposed to pure enantiomeric forms or racemic mix tures of 3H-labeled benzo(a)pyrene ani/or syn-7,8-dihydrodiol9,10-epoxide. Diol-epoxide-induced cytotoxicity and mutation frequencies at the hisG and gpt loci were determined. Hydrolysates of diol-epoxide-modified bacterial DMA were also examined by high-performance liquid chromatography and the primary structure and level of diol-epoxide-nucleoside adduci species were related to the observed frequencies of reverse mutations at the mutant hisG46 codon (histidine prototrophy) or forward mutations at the gpt locus (8-azaguanine resistance). Significant differences in mutagenic efficiency (i.e., mutation frequency per mol DNA adduci) were observed for the different enantiomeric diol-epoxides (-anti = ±syn», +anti) and Ihe mulagenic effi ciencies were Ihe same al bolh loci. The combined resulls of Ihe mulalion and adduci characterizalions suggesl lhal there are basic differences in the slructural configuralion of each adduci species which are recognized during errant DNA repair and as a result lead lo base changes al a frequency which is relalable lo the configuration of the original adduci lesion.