EFFECTS OF DIETARY INDOLE-3-CARBINOL ON ESTRADIOL METABOLISM AND SPONTANEOUS MAMMARY-TUMORS IN MICE
EFFECTS OF DIETARY INDOLE-3-CARBINOL ON ESTRADIOL METABOLISM AND SPONTANEOUS MAMMARY-TUMORS IN MICE
复制标题
DOI：
10.1093/carcin/12.9.1571
复制
发表时间：
1991-09-01
期刊：
影响因子：
4.7
通讯作者：
OSBORNE, MP
中科院分区：
文献类型：
--
作者：
BRADLOW, HL;MICHNOVICZ, JJ;OSBORNE, MP
吲哚-3-甲醇（I3 C）是包括人类在内的许多物种中细胞色素P450酶的有效诱导剂。因此，我们研究了不同品系的小鼠消耗I3 C在半合成粉末饲料中的剂量范围为250至5000 ppm（34-700 mg/kg/天）的不同时间内的雌二醇的细胞色素P450依赖性代谢的变化。在短期代谢研究（3周）中，SW和C3 H/OuJ小鼠的湿肝重量以剂量反应方式增加。膳食I3 C增加肝微粒体中测得的细胞色素P450含量，以及雌二醇2-羟基化的程度，高达5倍。在长期喂养实验（8个月）中，雌性C3 H/OuJ小鼠食用含I3 C的合成饲料（0、500或2000 p. p.m.）。两种I3 C剂量组的乳腺肿瘤发病率和多样性均显著降低，高剂量组的肿瘤潜伏期延长。我们的结论是，I3 C是一种诱导剂的肝脏P450依赖性雌激素代谢的小鼠，它是化学预防的C3 H/OuJ小鼠乳腺肿瘤模型。这种保护作用可能部分通过增加2-羟基化和随后的内源性雌激素失活来介导。
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. Dietary 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 high-dose group. We conclude that I3C is an inducer of hepatic P450-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.