EFFECTS OF INDOLE-3-CARBINOL ON THE METABOLISM OF 4-(METHYLNITROSAMINO)1-(3-PYRIDYL)-1-BUTANONE IN SMOKERS

Indole-3-carbinol (I3C) is a component of the human diet, occurring as a conjugate in certain cruciferous vegetables, I3C protects against c arcinogenesis in a variety of animal models by modifying carcinogen me tabolism, In mice, I3C decreases lung tumor formation by the tobacco-s pecific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NN K) by enhancing its hepatic clearance (M. A, Morse et al., Cancer Res. , 50: 2613-2617, 1990), In this study, our goal was to determine wheth er I3C would have similar effects on NNK metabolism in smokers as it d id in mice, Thirteen women took 400 mg of I3C on 5 consecutive days an d maintained constant smoking habits during this period, Their urine w as analyzed before and after the I3C treatment period for two metaboli tes of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and i ts glucuronide (NNAL-Gluc), I3C treatment resulted in decreased levels of urinary NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc, and increased NN AL-Gluc:NNAL ratio in 10 of the 13 women, The mean decreases in NNAL ( -0,27 +/- 0.09 pmol/mg creatinine, -23.4%) and NNAL plus NNAL-Gluc (-0 ,43 +/- 0.16 pmol/mg creatinine, -10.9%) were statistically significan t as was the increase in NNAL-Gluc:NNAL ratio (1.1 +/- 0.5, 39.9%), Th ese changes in urinary metabolites of NNK were consistent with those s een in mice treated with I3C and NNK; they suggest that I3C increased hepatic metabolism of NNK in our smokers, This is the first study to e xamine the effects of I3C on metabolism of an exogenous carcinogen in humans.