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.
Schmoldt
A
A
Institut für Rechtsmedizin, Universität Hamburg.
Jacob
J
J
Grimmer
G
G
D000818:Animals; D001551:Benz(a)Anthracenes / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D008658:Inactivation, Metabolic; D007262:Infusions, Intravenous; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats
D001551:Benz(a)Anthracenes; D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene