Effects of watercress consumption on urinary metabolites of nicotine in smokers

The effects of watercress consumption on the metabolism of nicotine in smok ers were examined. Watercress is a rich source of phenethyl isothiocyanate (PEITC), an effective chemopreventive agent for cancers of the lung and eso phagus induced in rodents by nitrosamines, including the tobacco-specific c arcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, PEITC is believed to inhibit nitrosamine carcinogenesis in rodents by inhibiting specific cy tochrome P450 (P450) enzymes. Among the P450s involved in the activation of these nitrosamines are members of the 2A family, P450 2A6 is believed to b e involved in the metabolism of both nicotine and its major metabolite coti nine, Therefore, we hypothesized that watercress consumption might inhibit nicotine and cotinine metabolism in smokers. The urine samples analyzed in this study were the same ones that we used in an earlier study (S, S, Hecht et al, Cancer Epidemiol, Biomark, Prev., 4: 877-884, 1995), in which we sh owed that watercress consumption increased levels of two metabolites of 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone: NNAL and its glucuronide NNAL -Gluc, This increase was attributed either to inhibition of cytochromes P45 0 or induction of glucuronidation, In the present study, we quantified urin ary nicotine and seven of its metabolites. There were no effects of watercr ess consumption on levels of nicotine, cotinine, trans-3'-hydroxycotinine, 4-oxo-4-(3-pyridyl)butanoic acid, or 4-hydroxy-4-(3-pyridyl)butanoic acid, indicating either that watercress ingestion has little effect on the oxidat ive metabolism of nicotine (presumably by P450 2A6 or other P450 enzymes) o r that these enzymes are not important for nicotine and cotinine metabolism in smokers. However, watercress consumption resulted in a significant incr ease compared to baseline levels of the glucuronides of cotinine (25%, P = 0.031) and trans-3'-hydroxycotinine (33%, P = 0.043) during the period when it was consumed and in a nonsignificant increase in levels of the glucuron ide of nicotine. These levels returned to baseline values after the watercr ess consumption period. There was a correlation between increases in levels of the glucuronides of trans-3'-hydroxycotinine and NNAL in the same subje cts, suggesting the involvement of a common enzyme. Thus, the results of th is study suggest that PEITC or another component of watercress induces UDP- glucuronosyltransferase activity in humans.