Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated with N-ethyl-N'-nitro-N-nitrosoguanidine, with induction of cytochrome P450s in the liver and consequent modulation of estrogen metabolism

Carcinogenesis
M YoshidaA Maekawa

Abstract

Indole-3-carbinol (I3C), found in cruciferous vegetables, has been shown to suppress or promote carcinogenesis depending on various animal models. Regarding its preventive effects, I3C acts as an anti-estrogen and can induce apoptosis, but precise mechanisms remain to be determined. Since I3C induces cytochrome P450 enzymes in the liver, it affects hydroxylation of estrogens and might therefore be expected to influence endometrial adenocarcinoma development. The present study was performed to clarify the effects of I3C using a rat two-stage endometrial carcinogenesis model, focusing on induction of cytochrome P450s and other estrogen-metabolic enzymes in the liver. First, to determine the estrogenic or anti-estrogenic activity, an uterotropic assay was conducted using ovariectomized Donryu rats (experiment 1). Second, to elucidate the effects on endometrial carcinogenicity, female Donryu rats initiated with a single dose of N-ethyl-N'-nitro-N-nitrosoguanidine into a uterine horn were fed 0 or 500 p.p.m. I3C in diets for 12 months (experiment 2). In experiment 3, similarly initiated animals received 0 or 2000 p.p.m. I3C in their diet, or 1 microg/kg 17beta-estradiol (E2) or 5 microg/kg 4-hydroxyestradiol (4HE) subcutaneously twi...Continue Reading

Citations

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