Mutation at separate gene loci in Salmonella typhimurium TA100 related to DNA nucleotide modification by stereoisomeric benzo (a) pyrene 7,8-diol-9,10-epoxides
Burgess, J.A.; Stevens, C.W.; Fahl, W.E.
Cancer Research 45(9): 4257-4262
1985
ISSN/ISBN: 0008-5472 PMID: 3928153 Document Number: 259054
Suspensions of Salmonella typhimurium TA100 or TA1535 cells were exposed to pure enantiomeric forms or racemic mixtures of 3H-labeled benzo(a)pyrene anti- or syn-7,8-dihydrodiol-9,10-epoxide. Diol-epoxide-induced cytotoxicity and mutation frequencies at the hisG and gpt loci were determined. Hydrolysates of diol-epoxide-modified bacterial DNA were also examined by high-performance liquid chromatography and the primary structure and level of diol-epoxide-nucleoside adduct 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 adduct) were observed for the different enantiomeric diol-epoxides (-anti = +/- syn much greater than, + anti) and the mutagenic efficiencies were the same at both loci. The combined results of the mutation and adduct characterizations suggest that there are basic differences in the structural configuration of each adduct species which are recognized during errant DNA repair and as a result lead to base changes at a frequency which is relatable to the configuration of the original adduct lesion.