Stimulation of drug and carcinogen metabolism by prolonged oral tobacco consumption.

Oral administration of tobacco to rats for 21 days caused remarkable stimulation of the metabolism of phenacetin, aniline and benzo[a]pyrene, a carcinogen, by hepatic microsomal mixed function oxidases (MFO). Such treatment for 6 days resulted in a small increase in the activities of phenacetin O-dealkylase and aromatic hydrocarbon hydroxylase (AHH) without affecting aniline hydroxylase activity. Nicotine given orally was found to be a relatively weak inducer of phenacetin O-dealkylase and aniline hydroxylase, and elicited a maximum increase in their activities within 6 days which remained unchanged even after 21 days of continuous administration. However, these two enzyme systems were not affected following only one or two doses of tobacco and nicotine. Both tobacco and nicotine inhibited these biotransformations in vitro.