The metabolism of 1-hydroxy- and 2-hydroxy-3-methylcholanthrene by liver microsomes: effect of enzyme inducing agents

The metabolism of both 1-hydroxy-3-methylcholanthrene (1-OH-3-MC) and 2-hydroxy-3-methylcholanthrene (2-OH-3-MC) by rat liver microsomes was investigated. Metabolites were separated by high pressure liquid chromatography (HPLC). Both compounds were shown to be substrates for further metabolism. Metabolism of 1-OH-3-MC gave rise to at least 13 products while 2-OH-3-MC showed the formation of at least 10 metabolites. At least 3 products of the 1-OH-3-MC metabolism are diol derivatives of the substrate. Using 2-OH-3-MC as substrate generated one major diol derivative that represented between 20% and 50% of total metabolite formation. Pretreatment of animals with known microsomal enzyme inducing agents did not result in the expected induction patterns. In some instances, the microsomes from induced animals were less efficient at metabolizing substrate than those from control. The discovery of a major peak from 2-OH-3-MC metabolism is of extreme importance considering the potency of the parent hydroxy compound in tumor initiation studies.