3-Hydroxymethylcholanthrene: metabolic formation from 3-methylcholanthrene and stereoselective metabolism by rat liver microsomes.

3-Hydroxymethylcholanthrene (3-OHMC) was identified as one of the three initial hydroxylation products formed in the metabolism at the aliphatic carbons of 3-methylcholanthrene (3MC) by rat liver microsomes. The 3-OHMC formed in 3MC metabolism by liver microsomes prepared from untreated (control) rats, and rats treated with phenobarbital, 3MC, and polychlorinated biphenyls (Aroclor 1254) was determined by HPLC analysis and the effect of enzyme inducers on its formation was phenobarbital > polychlorinated biphenyls > 3MC > control. Incubation of 3-OHMC with rat liver microsomes produced the following identifiable products: 1-hydroxy-3-hydroxymethylcholanthrene (enriched in 1S-enantiomer, enantiomer excess 14-50%), 2-hydroxy-3-hydroxymethylcholanthrene (enriched in 2S-enantiomer, enantiomer excess 30-92%), 3-hydroxymethylcholanthrene-1-one, 3-hydroxymethylcholanthrene-2-one, 8-hydroxy-3-hydroxymethylcholanthrene, 3-hydroxymethylcholanthrene trans-9,10-dihydrodiol (enriched in 9R,10R-enantiomer, enantiomer excess 64-86%), 3-hydroxymethylcholanthrene trans-7,8-dihydrodiol (enriched in 7R,8R-enantiomer), and 3-hydroxymethylcholanthrene trans-11,12-dihydrodiol (enriched in 11R,12R-enantiomer). The enantiomer compositions were determined by circular dichroism spectral analysis and/or chiral stationary phase HPLC analysis.