Covalent Bonding of Bay-Region Diol Epoxides to Nucleic Acids

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Abstract
Fifteen years ago, we proposed bay-region diol epoxides as the reactive metabolites responsible for the tumorigenic activity of polycyclic aromatic hydrocarbons (Jerina and Daly, 1976; Jerina et al., 1976; Jerina and Lehr, 1977). In the intervening period, extensive studies from several laboratories have provided substantial evidence that over a dozen hydrocarbons are activated by this pathway (Jerina et al., 1984; Lehr et al., 1985; Thakker et al., 1985). Examples have been forthcoming from a variety of structural types including benz- and dibenzanthracenes and acridines, benz- and dibenzpyrenes, chrysenes, and benzo[c]phenanthrene. To date, there are no known examples of carcinogenic alternant polycyclic aromatic hydrocarbons for which a bay-region diol epoxide is not an ultimate carcinogen. Although a number of mechanistically attractive alternatives to bay-region diol epoxides exist (Watabe et al., 1989; Cavalieri and Rogan, 1985; Miller et al., this volume), the extent of their contribution to the overall carcinogenicity of the hydrocarbons remains to be established.

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