Tumorigenicity of bay-region epoxides and other derivatives of chrysene and phenanthrene in newborn mice.

nogenic activity (4). Chrysene, which has one more benzene ring than does phenanthrene, is a symmetrical molecule with 2 identical bay regions (Chart 1). Chrysene has weak activity in carcinogenicity tests (4, 11). Quantum mechanical aspects of the bay region theory predict (6) that bay-region 1,2-diol 3,4-epoxides of chrysene and phenanthrene should have sim ilar chemical reactivities. Kinetic studies of their solvolysis in water from pH 2 to 10 have established that this is indeed the case (19). Since the calculations also predict that these 1,2diol-3,4-epoxides should be the most reactive of the possible isomemicbenzo-ningdiol-epoxides of the 2 hydrocarbons, these diol-epoxides and their dihydrodiol precursors are prime can didates as ultimate and proximate carcinogens, respectively (5, 6). In a bacterial mutagenicity test, chrysene 1,2-dihydmodiol3 was metabolically activated by hepatic enzymes to products that were 20 times more mutagenic to strain TA 100 of Sal monella typhimurium than were the metabolites formed from chmysene,chrysene 3,4-dihydrodiol, or chrysene 5,6-dihydro diol (24). When the double bond in the 3,4-position of chrysene 1,2-dihydrodiol was saturated, the resultingtetrahydrodiol could not be metabolically activated to mutagenic metabolites. In a study of the tumor-initiating activities of chrysene and its 3 metabolically possible dihydmodiolson mouse skin, chrysene 3,4and 5,6-dihydrodiol had no significanttumorigenic activity, but chrysene 1,2-dihydrodiol had about twice the tumonigenic activity of the parent hydrocarbon (11). When the double bond in the 3,4-positionof chrysene1,2-dihydrodiolwas saturated, the resulting tetrahydrodiol had less than 25% of the tumomi genic activity of chrysene 1,2-dihydrodiol. These results mdi cate that chrysene 1,2-dihydrodiol is a proximate carcinogenic metabolite and suggest that the 3,4-position of the molecule is a critical site for further metabolism to an ultimate carcinogenic metabolite.