Differences in mutagenicity and cytotoxicity of (+)- and (-)-benzo[a]pyrene 4,5-oxide: a synergistic interaction of enantiomers.
In order to study the biological effects of (+)- and (-)-benzo[a]pyrene 4,5-oxide, a synthesis of these molecules has been developed based on the resolution of (+/-)-cis-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene. The (-) 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 cells. In studies with V79 Cells, the (-) 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 (-) and (+) enantiomers of benzo[a]pyrene 4,5-oxide, respectively.
D000818:Animals; D001580:Benzopyrenes / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003603:Cytotoxins; D004357:Drug Synergism; D004852:Epoxy Compounds; D007536:Isomerism; D009153:Mutagens; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D001580:Benzopyrenes; D003603:Cytotoxins; D004852:Epoxy Compounds; D009153:Mutagens