Effect of nicotine and tobacco-specific nitrosamines on the metabolism of N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone by rat oral tissue

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Abstract
The effect of N''-nitrosoanatabine (NAT) and nicotine on the metabolism of N''-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by cultured rat oral tissue was investigated. The effect of NNN on NNK metabolism and the effect of NNK on NNN metabolism was also determined. NNK inhibited NNN metabolism more than NNN inhibited NNK metabolism. NAT inhibited the metabolism of NNK but not of NNN. Nicotine, which is present at > 500 times the level of NNN and NNK in smokeless tobacco, inhibited the metabolism of both nitrosamines. Inhibition of 1 .mu.M NNN metabolism was greater than that of 1 .mu.M NNK when the concentration of nicotine was 1, 10 or 100 .mu.M. Nicotine at 100 .mu.M inhibited the formation of all metabolites of NNN by 85-92%. These results suggest that NNN and nicotine may be metabolized by a common enzyme.