Nagao, M; Sugimura, T; Yang, SK; Gelboin, HV
HEEP COPYRIGHT: BIOL ABS. Benzo(a)pyrene (BP) is 1 of the carcinogens that is ubiquitous in the environment. Bacterial mutation tests may be useful for the primary screening of carcinogens and for the detection of ultimate or proximate forms of muta carcinogens. The mutagenicity of various BP derivatives has been reported by many researchers. r-7,t-8-Dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene(diol-epoxide I), r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene(diol-epoxide II) and 4,5-oxy-4,5-dihydrobenzo (a)pyrene were the strongest direct mutagens (3,4,10). trans-7,8-Dihydroxy-7,8-dihydrobenzo(a)pyrene(trans-7,8-diol) was a more potent mutagen than BP when metabolically activated by mammalian cells in culture or by highly purified hepatic microsomal enzymes from rats. These findings are consistent with the observation that trans-7,8-diol is converted metabolically into diol-epoxides I and II, which were the most active direct mutagens. In rats, one of the diastereomers of diol-epoxide I was produced in vitro exclusively from the (-)-enantiomer of trans-7,8-diol (16). The (+)- and (-)-enantiomers of trans-7,8-diol have been resolved as their di(-)-menthoxyacetates by high pressure liquid chromatography. This paper reports on the mutagenicity of the (+)- and (-)-enantiomers of trans-7,8-diol, their di (-)menthoxyacetates, and the hydrolysis and reduction products of diol-epoxides I and II. (Salmonella typhimurium was used.)