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 nitro samine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was studie d in rats. [1-C-14]NNK was s.c. injected at a dose of 0.08 mu mol/kg. Co-administration of a 500-fold higher dose of nicotine (40 mu mol/kg) did not reduce the overall urinary excretion of radioactivity. Howeve r, the metabolic pattern in 24 h urine was significantly changed. Meta bolites resulting from NNK activation by alpha-hydroxylation were sign ificantly (P < 0.001) reduced to 72% of the control. Detoxification to N-oxides and the glucuronide of 4-(methylnitrosamino)-1-(3-pyridyl)-1 -butanol increased to 155% (P < 0.01) and 188% (P < 0.01) of the contr ol respectively. These results suggest that nicotine, which occurs in concentrations up to 30 000-fold higher than NNK in mainstream smoke o f cigarettes may have a protective effect against metabolic activation of NNK.