THE GENOTOXIC POTENTIAL OF NICOTINE AND ITS MAJOR METABOLITES

Nicotine is a naturally occurring alkaloid found primarily in members of the solanaceous plant family, which includes tobacco, Nicotine is r apidly absorbed by humans and then metabolized, primarily by cytochrom e P450's. Studies on the genotoxic potential of these metabolites are limited, Nicotine and four of its major metabolites: cotinine, nicotin e-N'-oxide, cotinine-N-oxide, and trans-3'-hydroxycotinine were evalua ted for genotoxic potential in the Salmonella mutagenicity assay (stra ins TA98, TA100, TA1535, TA1537, and TA1538) at concentrations ranging from 0 to 1000 mu g/plate and in the Chinese hamster ovary sister-chr omatid exchange (SCE) assay at concentrations ranging from 0 to 1000 m u g/ml. All assays were conducted with and without S9 metabolic activa tion. None of the five compounds increased the frequency of mutations or the frequency of SCEs, These results indicate that nicotine and its major metabolites are not genotoxic in the assays conducted.