9,10-Dihydroxy-9,10-dihydro-3-methylcholanthrene-2-one: a principal metabolite of the potent carcinogen 3-methylcholanthrene-2-one by rat liver microsomes.

A principal metabolite, formed in the metabolism of the potent carcinogen 3-methylcholanthrene-2-one (3MC-2-one) by liver microsomes from either untreated, or phenobarbital-treated or 3-methylcholanthrene (3MC)-treated rats, was isolated by reversed-phase HPLC. This metabolite has been identified as a 9,10-dihydrodiol with a (9R,10R):(9S,10S) enantiomer ratio of approximately 84:16 by all three rat liver microsomal preparations. The 9,10-dihydrodiol metabolite and its NaBH4 reduction products [a pair of diastereomeric 9,10-dihydroxy-9, 10-dihydro-2-OH-3MC (2-OH-3MC 9,10-dihydrodiols)] were characterized by UV-visible absorption, mass, and circular dichroic spectral, and chiral stationary phase HPLC analyses. Identification of 9,10-dihydroxy-9,10-dihydro-3MC-2-one (3MC-2-one 9,10-dihydrodiol) as the predominant metabolite of the potent carcinogen 3MC-2-one suggests that 3MC-2-one may be metabolically activated to a bay region 9,10-diol-7,8-epoxide, similar to the previously established metabolic activation pathways of 3MC and 1-hydroxy-3-methylcholanthrene (1-OH-3MC).