Synthesis and mutagenicity of 5-alkyl-substituted chrysene-1,2-diol-3,4-epoxides.
In order to explore the relationship between structure and mutagenicity of bay region diol-epoxides of chrysene substituted with an alkyl group in the bay region, we compared the mutagenicity in Salmonella typhimurium TA 100 of anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene with its 5-methyl, 5-ethyl and 5-propyl derivatives. The results showed that anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (7400 revertants/nmol) was the most mutagenic of these diol-epoxides followed by anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene and its 5-ethyl derivative (1100 revertants/nmol). The 5-propyl substituted diol-epoxide was inactive at the doses tested. The results demonstrate that steric factors are dominant in the expression of methylchrysene diol-epoxide mutagenicity in S. typhimurium and suggest that the molecular shape of the 5-methyl substituted diol-epoxide leads to a unique reaction with DNA associated with high mutagenicity and tumorigenicity.
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Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, NY 10595.
Huie
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Balanikas
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Hecht
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D002911:Chrysenes / Q000138:chemical synthesis / Q000633:toxicity*; D009153:Mutagens / Q000138:chemical synthesis*; D010616:Phenanthrenes / Q000633:toxicity*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002911:Chrysenes; D009153:Mutagens; D010616:Phenanthrenes; C021977:chrysene,2-diol-3,4-epoxide-1