Metabolism of benz(a)anthracene catalyzed by liver microsomes of untreated and nicotine-pretreated rats.
The purpose of the present investigation was to determine whether nicotine causes an induction or alteration of rat liver microsomal monooxygenases (cytochromes P-450) involved in the metabolism and activation of polycyclic aromatic hydrocarbons. After 2, 4, and 10 days of continuous nicotine treatment (16.8 mg/day) neither an increase of benz(a)anthracene metabolism nor an alteration of the metabolite pattern could be observed in comparison to controls. Moreover, there was no significant change of cytochrome P-450 content or benzo(a)pyrene hydroxylation rates. In further control experiments the inducibility of the rats was tested by pretreatment with benzo(k)fluoranthene. As expected, this treatment resulted in a high increase of metabolism and the formation of the ultimate carcinogen as well as other metabolites of benz(a)anthracene due to the induction corresponding to isocytochrome P-450. For nicotine it can be concluded that this alkaloid cannot cause qualitative or quantitative changes of normal rat liver cytochromes P-450.