Consumption of watercress fails to alter coumarin metabolism in humans

Watercress is an excellent source of phenethyl isothiocyanate (PEITC), an e ffective inhibitor of nitrosamine carcinogenesis in rodents, The mechanism of inhibition is believed to be due in part to inhibition of cytochrome P45 0 (P450) enzymes, P450 2A6 is a catalyst for the metabolic activation of se veral nitrosamines. In this study, we investigated the effect of watercress consumption on coumarin 7-hydroxylation, a P450 2A6-specific reaction, in a group of 15 nonsmoking, healthy volunteers. The urinary excretion of 7-hy droxycoumarin (7OHC) was determined, For 6 of the 15 subjects, watercress c onsumption decreased the amount of 7OHC excreted in the first 2 h following coumarin administration, However, the mean 0- to 2-h excretion of 7OHC for all 15 subjects was not significantly lowered by the consumption of waterc ress, 2.8 +/- 0.78 versus 3.1 +/- 0.53 mg (+/-S.D.). The mean 7OHC excreted from 2 to 4 h (1.1 +/- 0.50 mg) was significantly higher (P = 0.027) durin g watercress consumption than before (0.77 +/- 0.22 mg), suggesting a delay in coumarin metabolism. Total excretion of 7OHC was unaffected by watercre ss consumption, Therefore, under the conditions of our study, PEITC and oth er constituents of watercress had at most a marginal inhibitory effect on P 450 2A6-catalyzed coumarin 7-hydroxylation.