Polycyclic aromatic hydrocarbons (PAH) are known to require metabolic activation to reactive electrophilic forms (ultimate mutagens and carcinogens) before they exert their toxic, mutagenic and carcinogenic properties. """"""""Bay region"""""""" diol epoxides are now generally recognized as a very important class of ultimate carcinogen for PAH, and the relationship of diol epoxide structure to their relative mutagenicity and carcinogenicity is one factor that must be understood before PAH carcinogenicity can be understood. Currently, virtually nothing is known of te role of diol epoxides in the carcinogenicity of aza-PAH such as the benz- and dibenzacridines, and of the structural factors affecting their relative mutagenicity and carcinogenicity. Synthesis of potential proximate and carcinogenic metabolites of the strong carcinogen dibenz[c,h]acridine and comparison of their mutagenic and tumorigenic behavior with that of the analogous PAH will help to elucidate whether bay region diol epoxides are important in the mutagenesis and carcinogenesis of aza-PAH and how nitrogen substitution affects these biological properties. Similarly, almost no direct evidence is available concerning the magnitude and nature of the effect of methyl substitution on the mutagenic and carcinogenic properties of diol epoxides, although indirect evidence indicates that it can be substantial. A series of tetrahydroepoxides derived from benzo[a]anthracene with epoxide substitution on the angular ring and methyl substitution on the aromatic nucleus will be prepared to determine the effect. The bay region diol epoxides of 7,12-dimethylbenzo[a]anthracene (DMBA), which are strongly implicated as ultimate carcinogens of DMBA will be synthesized via a novel approach. The effect of structure on the solvolytic reactivity of te epoxide will also be determined, and compared with expectations based upon molecular orbital calculations.
