Chem -Bwl Interactwns, 83 (1992) 155 - 169 155 Elsevier Scmntlfic Pubhshers Ireland Ltd THE ANTI-CARCINOGENIC PLANT COMPOUND INDOLE-3-CARBINOL DIFFERENTIALLY MODULATES P450-MEDIATED STEROID HYDROXYLASE ACTIVITIES IN MICE WILLIAM S BALDWIN and GERALD A LEBLANC Department of Toxicology, Box 7633, North Carohna State Unwers~ty, Raleigh, NC 27695 (USA) (Received March 3rd, 1992) (Rewsmn received April 14th, 1992) (Accepted April 14th, 1992) SUMMARY Indole-3-carbmol (I3C), a component of cruclferous vegetables, exhibits anti- carcinogenic activity m a variety of model systems This activity has been attributed m part to the reduction of cytochrome P450 CYP1A subfamily members and the resulting mcreased metabohc mactlvatmn of chemmal carcino- gens The present study was undertaken to assess the effects of I3C on several constitutive P450 actlvltms that contribute to both carcinogen and stermd hor- mone metabohsm Mxce were administered I3C m their diet at estimated dally doses of 250, 500 and 750 mg/kg for 1 week Liver mmrosomes from treated and untreated mine were subsequently assayed for CYPIA-medmted ethoxy- resorufin O-deethylase (EROD) actlwty, estradml 2-hydroxylase actavlty and seven different testosterone hydroxylase act~wtms I3C elevated EROD, estradlol 2-hydroxylase and testosterone 6a-hydroxylase actwltms m a dose- dependent manner The other SLX testosterone hydroxylase act~wtms were not slgmficantly affected by m wvo treatment with I3C In ad&tmn to its effects on steroid hydroxylase actlwtms, I3C also elevated NADPH-cytochrome P450 reductase actlwty, a necessary component to the P450 monooxygenase system We next examined the direct m wtro effects of I3C and its acid condensatmn products, as are generated in the stomach following mgestmn, on the P450 catalytm actlvxtms Testosterone 6~-hydroxylase, the major testosterone hydroxylase actlwty m untreated mine, was sxgmficantly inhabited (ICs0 - 12 #g/ml) by the acid condensatmn products of I3C In contrast, all other P450 actlwtms were not appreciably affected by I3C or its acid condensatmn products These results mdmate that I3C can ehclt both mductwe and suppressive effects on the constitutive P450s that partxclpate m carcinogen and steroid hormone metabohsm This plelotropm effect on hepatm catalytm enzymes may contnbute to the ante-carcinogenic properties of th~s compound Correspondence to G A LeBlanc, Department of Toxmology, Box 7633, North Carohna State Umverslty, Raleigh, NC 27695, USA 0009-2797/92/$05 00 © 1992 Elsewer Scmntlfic Pubhshers Ireland Ltd Pnnted and Pubhshed in Ireland