Many attentions have long been paid to the question about the reason why benz [a]-anthracene (BA), a very weak carcinogen, increases its carcinogenic activity to the level of the most potent carcinogenic hydrocarbons, such as benzo [a] pyrene (BP) and 3-methylcholanthrene (3-MC), by the substitution of methyl group(s) for the "L-region" (7-and 12-positions) hydrogens, e.g. 7, 12-dimethyl-BA (DMBA) has a higher carcinogenic activity than BP, and 7-methyl-BA (7-MBA) is as carcinogenic as 3-MC (Cavalieri, 1979; Selkirk, 1980). In addition, 3-MC is also an alkyl-substituted BA. The marked increase in carcinogenicity of aromatic hydrocarbons by a methyl substituent is observed not only with BA but also with other aromatic hydrocarbons, such as chrysene and anthrabene (Cavalieri, 1979; Selkirk, 1980). 5-Methylchrysene, for instance, has as highly carcinogenic activity as 3-MC whereas carcinogenicity of chrysese is very weak. Similarly, 9, 10-dimethylanthracene is carcinogenic whereas the mother compound; anthracene, is not carcinogenic (Fig. 1). Several attempts have been made to know active metabolites of DMBA in relation to epoxide formation. DMBA 5, 6-oxide has been isolated and identified as an active metabolite from a hepatic mitrosomal reaction mixture (Keysell et al., 1973). DMBA 3, 4-diol-1, 2-epokide was also strongly assumed to be an active metabolite, but has not been detected yet from the in vitro system (Jerina et al., 1978 ; Malaveille et al., 1978 ; Wislocki bt al:, 1980). These studies, however, were carried out by using liver microsomes from rats pretreated with the P-448 inducer, 3-MC or polychlorinated biphenyls. 8, 9- and 10, 11-epoxides of DMBA might also be candidates for the active metabolites since their hydrolysis products, 8, 9- and 10, 11-dihydrodiols, have been isolated from a rat liver microsomal system (DiGiovanni and Juchau, 1980).
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