Role of Cytochrome P-450 in the Bioactivation of Nicotine

Nicotine (100 .mu. M) was incubated with microsomes (1 mg/ml) prepared from New Zealand White rabbits. On the basis of microsomal weight, the rate of nicotine oxidation were calculated on the basis of cytochrome P-450 concentration, the specific activity of the metabolic oxidation catalyzed by lung was approximately 4 times greater than liver (6.4 vs 1, 65 nmoles nicotine oxidized. nmole cytochrome $P-450^{-1}\;min{-1})$. These studies employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme2 and 6 specific inhibitor $\alpha$-methylbenzyl ABT, metabolite inhibitors, norbenzphetamine and N-hydroxyamphetamine. TCDD induction and Arochlor 1260 pretreatment. These results support the conclusion that nicotine metabolism by rabbit lung microsomes is mediated primarily by cytochrome P-450 isozyme 2.