Journal
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
Volume 36, Issue 1, Pages 112-121Publisher
ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
DOI: 10.1207/S15327914NC3601_15
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Funding
- NATIONAL CANCER INSTITUTE [R01CA069056] Funding Source: NIH RePORTER
- NCI NIH HHS [CA-69056] Funding Source: Medline
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The well-documented reduction of cancer risk by high dietary cruciferous vegetable intake may in part be caused by modulation of cytochrome P-450 (CYP) expression and activity by indoles. The purpose of the present experiments was to study the mechanism of CYP 1A1 induction by N-methoxyindole-3-carbinol (NI3C) in cultured cells and to compare the CYP-inducing potential of NI3C and indole-3-carbinol (I3C) administered to rats. NI3C induced 7-ethoxyresorufin-O-deethylase (EROD) activity in Hepa-1c1c7 cells in a concentration-dependent manner with 10-fold higher efficiency than I3C. Inasmuch as NI3C induced binding of the aryl hydrocarbon receptor (AhR) to the dioxin-responsive element and induced expression of endogenous CYP 1A1 mRNA and an AhR-responsive chloramphenicol acetyl transferase construct, we conclude that NI3C can activate the AhR. Besides the induction of CYP 1A1, we observed an inhibition of EROD activity, with a concentration causing 50% inhibition of 6 mu M. Oral administration of NI3C at 570 mu mol/kg body wt to male Wistar rats increased the hepatic CYP 1A1 and 1A2 protein levels, as well as the EROD and 7-methoxyresorufin O-demethylase activities at 8 and 24 hours after administration, but the responses were less pronounced than after administration of I3C at 570 mu mol/kg body wt. Furthermore, NI3C did not induce hepatic 7-pentoxyresorufin O-depentylase activity, as I3C did. Ascorbigen, another indolylic compound formed during degradation of glucobrassicin in the presence of ascorbic acid, was tested in the same animal model, and ascorbigen only weakly induced hepatic CYP 1A1 and 1A2, but not CYP 2BI/2. In conclusion, NI3C is a more efficient inducer of CYP 1A1 in cultured cells than I3C but is less active when administered to rodents.
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