The metabolism of 3-methylcholanthrene by liver and lung microsomes: Effect of enzyme inducing agents

doi:10.1016/0304-3835(83)90031-9

Cancer Letters

Volume 20, Issue 3, October 1983, Pages 323-331

https://doi.org/10.1016/0304-3835(83)90031-9 Get rights and content

Abstract

The metabolism of 3-methylcholanthrene (3-MC) by rat liver and lung microsomes was investigated. The animals were pretreated with various inducing agents to determine the effect which microsomal induction has on metabolic profile. Metabolites were separated by high pressure liquid chromatography. Major metabolism was associated with three peaks: 2-hydroxy-3-MC, 1-hydroxy-3-MC and a peak that co-chromatographs with 3-MC 11,12-oxide and probably contains phenols. Pretreatment of animals with various inducing agents caused an increase in total metabolism as well as in specific metabolites. However, lung microsomes from phenobarbital treated animals were less efficient at metabolizing 3-MC than control microsomes. Liver and lung microsomes converted 3-MC to qualitatively similar products. No metabolites were formed by lung microsomes that were not also formed by those from liver.

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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.
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Research letterThe metabolism of 3-methylcholanthrene by liver and lung microsomes: Effect of enzyme inducing agents

Abstract

Chem.-Biol. Interact.

J. Biol. Chem.

FEBS Lett.

Life Sci.

Tumorigenic activity of 3-methylcholanthrene metabolites on mouse skin and in newborn mice

Cancer Res.

In vitro malignant transformation of mouse fibroblasts by non-K-region dihydrodiols derived from 7,12-dimethylbenz(a) anthracene and benzo(a)pyrene

Cancer Res.

Research letter
The metabolism of 3-methylcholanthrene by liver and lung microsomes: Effect of enzyme inducing agents