Kojima T, Tanaka T, Mori H
First Department of Pathology, Gifu University School of Medicine, Japan.
Cancer Res. 1994 Mar 15;54(6):1446-9.
Indole-3-carbinol (I3C) present in cruciferous vegetables has been found to inhibit chemically induced neoplasms in forestomach, mammary gland, liver, and tongue in rodents. I3C is also known to induce estradiol 2-hydroxylase and reduce estrogenic activity. The current study was conducted to examine the possible inhibiting effect of I3C on spontaneous occurrence of endometrial adenocarcinoma in female Donryu rats. The high incidence of endometrial cancer in this strain of rats might be related to increased estrogen/progesterone ratio with aging. A total of 141 female Donryu rats were divided into four groups. Group 1 was given a basal diet alone throughout the study. Starting at 6 weeks of age, groups 2-4 were respectively given the diets containing 200, 500, and 1000 ppm I3C for the entire experimental period (660 days). At the termination of the experiment, the incidences of preneoplastic lesions and neoplasms in the endometrium were estimated. Also, estradiol 2-hydroxylation activity in the liver was assayed in rats fed I3C at these doses for 3 weeks. The incidences of endometrial adenocarcinoma in rats fed I3C [8 of 32 rats (25%) in group 2, 5 of 32 rats (16%) in group 3, and 5 of 35 rats (14%) in group 4] were respectively smaller than that in group 1 (12 of 32 rats, 38%). The incidence of uterine adenocarcinoma in group 4 was significantly lower than that in group 1 (P < 0.05). Dietary I3C also decreased the frequency of preneoplastic endometrial lesions (31% in groups 2-4 versus 44% in group 1). I3C exposure also inhibited the incidence of mammary fibroadenoma. Biochemical assay for estradiol 2-hydroxylation revealed that feeding of I3C significantly increased estradiol 2-hydroxylation (nmol/mg protein) compared to rats treated without I3C [0.34 +/- 0.04 in group 2, 0.53 +/- 0.13 in group 3, and 0.58 +/- 0.11 in group 4 versus 0.28 +/- 0.02 in group 1; P < 0.02, P < 0.003, and P < 0.001, respectively]. These results suggest that dietary I3C inhibits spontaneous occurrence of endometrial adenocarcinoma as well as preneoplastic lesions in Donryu rats. This chemopreventive effect of I3C may be due to its induction of estradiol 2-hydroxylation.
十字花科蔬菜中含有的吲哚 - 3 - 甲醇（I3C）已被发现可抑制啮齿动物前胃、乳腺、肝脏和舌头的化学诱导肿瘤。I3C还可诱导雌二醇2 - 羟化酶并降低雌激素活性。本研究旨在检测I3C对雌性唐育大鼠子宫内膜腺癌自发发生的可能抑制作用。该品系大鼠子宫内膜癌的高发病率可能与衰老导致的雌激素/孕激素比值增加有关。总共141只雌性唐育大鼠被分为四组。第1组在整个研究过程中仅给予基础饮食。从6周龄开始，第2 - 4组在整个实验期（660天）分别给予含200、500和1000 ppm I3C的饮食。实验结束时，估计子宫内膜中癌前病变和肿瘤的发生率。此外，对以这些剂量喂食I3C 3周的大鼠肝脏中的雌二醇2 - 羟化活性进行了测定。喂食I3C的大鼠子宫内膜腺癌的发生率[第2组32只大鼠中有8只（25%），第3组32只大鼠中有5只（16%），第4组35只大鼠中有5只（14%）]分别低于第1组（32只大鼠中有12只，38%）。第4组子宫腺癌的发生率显著低于第1组（P < 0.05）。饮食中的I3C还降低了子宫内膜癌前病变的频率（第2 - 4组为31%，而第1组为44%）。I3C暴露也抑制了乳腺纤维腺瘤的发生率。雌二醇2 - 羟化的生化分析表明，与未用I3C处理的大鼠相比，喂食I3C显著增加了雌二醇2 - 羟化（nmol/mg蛋白质）[第2组为0.34±0.04，第3组为0.53±0.13，第4组为0.58±0.11，而第1组为0.28±0.02；P分别< 0.02、< 0.003和< 0.001]。这些结果表明，饮食中的I3C可抑制唐育大鼠子宫内膜腺癌以及癌前病变的自发发生。I3C的这种化学预防作用可能是由于其诱导雌二醇2 - 羟化。
