Differences in mutagenicity and cytotoxicity of (+)- and (-)-benzo[a]pyrene 4,5-oxide: a synergistic interaction of enantiomers.

Abstract

To study the biological effects of (+)- and (.sbd.)-benzo[a]pyrene 4,5-oxide, a synthesis of these molecules was developed based on the resolution of (.+-.)-cis-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene. The (.sbd.) enantiomer of benzo[a]pyrene 4,5-oxide was 1.5- to 5.5-fold more mutagenic than the (+) enantiomer in strains TA 98, TA 100, TA 1537 and TA 1538 of Salmonella typhimurium and in Chinese hamster V79 [lung] cells. In studies with V79 cells, the (.sbd.) enantiomer of benzo[a]pyrene 4,5-oxide was also more cytotoxic than the (+) enantiomer. When mixtures of the enantiomers were studied in V79 cells, synergistic cytotoxic and mutagenic responses were observed. The greatest cytotoxic and mutagenic effects occurred with a 3:1 mixture of the (.sbd.) and (+) enantiomers of benzo[a]pyrene 4,5-oxide, respectively.