Synthesis and mutagenicity of 5-alkyl-substituted chrysene-1,2-diol-3,4-epoxides

In order to explore the relationship between structure and mutagenicityof bay region diol-epoxides of chrysene substituted with analkyl group in the bay region, we compared the mutagenicityin Salmonella typhimurium TA 100of anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysenewith its 5-methyl, 5-ethyl and 5-propyl derivatives. The resultsshowed that anti-l,2-dihydroxy-3,4-epoxy-l,2,3,4-tetrahydro-5-methylchrysene(7400 revertants/nmol) was the most mutagenic of these diol-epoxidesfollowed by anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochryseneand its 5-ethyl derivative (1100 revertants/nmol). The 5-propylsubstituted diol-epoxide was inactive at the doses tested. Theresults demonstrate that steric factors are dominant in theexpression of methylchrysene diol-epoxide mutagenicity in S.typhimuriumand suggest that the molecular shape of the 5-methyl substituteddiol-epoxide leads to a unique reaction with DNA associatedwith high mutagenicity and tumorigenicity.