Nicotine inhibits the metabolic activation of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats.

The effect of nicotine on the metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was studied in rats. [1-14C]NNK was s.c. injected at a dose of 0.08 mumol/kg. Co-administration of a 500-fold higher dose of nicotine (40 mumol/kg) did not reduce the overall urinary excretion of radioactivity. However, the metabolic pattern in 24 h urine was significantly changed. Metabolites resulting from NNK activation by alpha-hydroxylation were significantly (P < 0.001) reduced to 72% of the control. Detoxification to N-oxides and the glucuronide of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol increased to 155% (P < 0.01) and 188% (P < 0.01) of the control respectively. These results suggest that nicotine, which occurs in concentrations up to 30,000-fold higher than NNK in mainstream smoke of cigarettes may have a protective effect against metabolic activation of NNK.