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© 1991 Oxford University Press

research-article

Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice

H.Leon Bradlow, Jon J. Michnovicz 1, Nitin T. Telang 2 and Michael P. Osborne 2

The Institute for Hormone Research 145 East 32nd Street, Tenth Floor, New York, NY 10016
2The Breast Cancer Research Lahratory, Memorial Slaon-Kettering Cancer Center 1275 York Avenue, New York, NY 10021, USA

Indole-3-carbinol (I3C) is a potent inducer of cytochrome P450 enzymes in many species, including humans. We therefore studied alterations in the cytochrome P450-dependent metabolism of estradiol in different strains of mice consuming I3C in semisynthetic powdered diets at doses ranging from 250 to 5000 p.p.m. (34–700 mg/kg/day) for different periods of time. In short-term metabolic studies (3 weeks), wet liver weight increased in SW and C3H/OuJ mice in a dose-responsive manner. Dieiary I3C increased the cytochrome P450 content measured in hepatic microsomes, as well as the extent of estradiol 2-hydroxylation, up to 5-fold. In a long-term feeding experiment (8 months), female C3H/OuJ mice consumed synthetic diets containing I3C at 0, 500 or 2000 p.p.m. Mammary tumor incidence and multiplicity were significantly lower at both doses of I3C, and tumor latency was prolonged in the highdose group. We conclude that I3C is an inducer of hepatic P45O-dependent estrogen metabolism in mice, and that it is chemopreventive in the C3H/OuJ mouse mammary tumor model. This protective effect may be mediated in part by the increased 2-hydroxylation and consequent inactivation of endogenous estrogens.


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