INTRINSIC MUTAGENICITY AND ELECTROPHILICITY OF 1-SULFOOXY-3-METHYLCHOLANTHRENE - IMPLICATIONS FOR METABOLIC-ACTIVATION OF THE CARCINOGEN 3-METHYLCHOLANTHRENE

Hydroxylation of a meso-anthracenic carbon atom with subsequent format ion of a reactive eater bearing a good leaving group (e.g., sulfate) h as been proposed as a possible biochemical mechanism responsible for D NA binding, mutagenicity and tumorigenicity of 3-methylcholanthrene, o ne of the most potent carcinogenic polycyclic aromatic hydrocarbons in experimental animals. In support of this supposition, the chemically synthesized sulfuric acid ester, 1-sulfooxy-3-methylcholanthrene (1-SM C) was directly mutagenic in bacteria and covalently bound to DNA with out metabolic activation. The intrinsic mutagenicity of this reactive ester was significantly potentiated by addition of extra acetate or ch loride anions to the media. Reduced glutathione and ascorbic acid prot ected against 1-SMC-induced mutagenesis. These findings suggest 1-SMC as a potential ultimate electrophilic and tumorigenic metabolite of 3- methylcholanthrene.