The mechanism of microsomal hydroxylation of 7-methylbenz(a)-anthracene and 7,12-dimethylbenz(a)anthracene by oxygen-18 studies

The carcinogenic 7-methylbenza]anthracene and 7,12-dimethylbenza]anthracene were converted by rat liver microsomes into the corresponding hydroxymethyl derivatives and other metabolic products. The 7-methylbenza]anthracene incubation was carried out in H₂¹⁸O, and no incorporation of oxygen-18 was found in the hydroxymethyl metabolite isolated and purified by high pressure liquid chromatography, and analyzed by mass spectrometry. When 7-methylbenza]anthracene or 7,12-dimethylbenza]anthracene was incubated with ¹⁸O₂, isotope incorporation was observed in the corresponding hydroxymethyl derivatives, indicating that such hydroxylation is a true oxygenase reaction.