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.