Effect of Nicotine and Cotinine on NNK Metabolism in Rats

[5- 3H]-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was infused subcutaneously at a daily dose of 7.2 nmol/kg with or without 26 µmol/kg nicotine or cotinine, respectively, over four weeks in male F344 rats. Coadministration of nicotine or cotinine had no effect on the excretion of NNK and its metabolites. However, at the end of the experiment binding of radioactivity to hemoglobin in nicotine- and cotinine-treated rats was reduced by 50% compared to NNK-only treated rats. The inhibition of hemoglobin adduct formation by tobacco alkaloids may explain the lower than expected differences in the adduct levels of tobacco-specific nitrosamines between smokers and nonsmokers as observed in several biomonitoring studies.