Multiple regions of metabolic activation of carcinogenic hydrocarbons.

Abstract

SEVERAL lines of evidence have strongly implicated the bay region anti-diolepoxide of benzo(a)pyrene (BP) (Fig. 1) as the principal metabolically activated form of this potent environmental carcinogen1. A bay region is defined simply as a molecular region such as the 4,5-positions of phenanthrene. Recent studies indicate the bay region diolepoxides of 3-methyl-cholanthrene (3-MC) (refs 2, 3), benz(a)anthracene4,5, 7-methylbenz(a)anthracene (MBA) (ref. 6), 7,12-dimethylbenz(a)-anthracene (DMBA) (refs 7, 8), and dibenz(a, h)anthracene9 as the ultimate carcinogenic forms of these hydrocarbons. (In the cases of 3-MC, 7-MB A and 7,12-DMBA there is evidence for an additional benzylic hydroxyl group.) Jerina and Daly10 suggest, on the basis of simple molecular orbital calculations, that the bay region diolepoxides of carcinogenic polycyclic arenes are generally distinguished by exceptional reactivity and are the ultimately active forms of this class of carcinogen. We report here evidence for metabolites other than bay region diolepoxides as the active forms of at least some carcinogenic hydrocarbons.