Synthesis and mutagenicity of A-ring reduced analogs of 7,12-dimethylbenz[a]anthracene

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Abstract
The synthesis and mutagenicity of 2 derivatives of 7,12-dimethylbenz[a]anthracene (DMBA) are reported. These analogs represent dihydro and tetrahydro A-ring reduced forms of DMBA, a region in the parent hydrocarbon proposed to be involved in metabolism to the ultimate carcinogen. The synthesis for one of the derivatives without isolation of intermediates from the tosylhydrazone of 1,2,3,4-tetrahydrobenz[a]anthracene-4,7,12-trione by successive reaction with 8 M equivalents of CH3Li, HI and NaBH4 represents a novel approach to this hydrocarbon now available in sufficient quantity for biological studies. Interestingly, both reduced analogs exhibited mutagenic activity in the Ames assay in the presence or absence of [mammalian] microsomal activation for [Salmonella typhimurium] strains TA98 and TA100. In these strains, DMBA was active only in the presence of S9 fraction. In the plasmid-deficient strain TA1537, only the tetrahydro analog exhibited mutagenic activity both in the absence and presence of S9 fraction.

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