Oganesian A, Hendricks J D, Williams D E
Department of Food Science, and the Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, 97331-6602, USA.
Cancer Lett. 1997 Sep 16;118(1):87-94. doi: 10.1016/s0304-3835(97)00235-8.
Indole-3-carbinol (I3C), a natural component from cruciferous vegetables, has been demonstrated to be a modulator of carcinogenesis in various animal models. Along with the promising perspectives of I3C as a possible chemopreventive agent for human breast cancer, some concerns have been raised regarding the tumor-promotional potency of this compound in other target organs. In this study we examined the hepatic tumor-modulatory properties of I3C fed to C57BL/6J mice, initiated with diethylnitrosamine (DEN). Infant male mice were initiated with 0, 2 or 5 mg/kg DEN (i.p. injection) at 15 days of age. Mice were weaned 9 days later and immediately put on AIN76A semipurified diet (with no antioxidants) containing 0 or 0.15% (1500 ppm) I3C. In addition, at the age of 2 months, one group of mice initiated with 2 mg/kg DEN was injected i.p. with a single dose (20 mg/kg) of 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), to serve as a positive control group for promotion. Mice were sampled for hepatic tumors at the age of 6 or 8 months. Each sampled group contained 11-12 mice except the HCB group (nine animals). After 8 months, there was a statistically significant (P < 0.0005) inhibition of hepatocarcinogenesis observed for I3C-fed animals initiated with the high dose of DEN. A single injection of HCB at 2 months of age significantly (P = 0.0003) enhanced hepatocarcinogenesis in mice initiated with 2 mg/kg DEN. There was no statistically significant difference between groups sampled at 6 months of age. Our observations indicate that long term administration of I3C in the diet inhibits DEN-initiated hepatocarcinogenesis in the infant mouse model.
吲哚 - 3 - 甲醇（I3C）是十字花科蔬菜中的一种天然成分，在多种动物模型中已被证明是致癌作用的调节剂。随着I3C作为人类乳腺癌潜在化学预防剂的前景看好，人们对该化合物在其他靶器官中的促肿瘤潜力也提出了一些担忧。在本研究中，我们检测了喂食I3C的C57BL / 6J小鼠的肝脏肿瘤调节特性，这些小鼠用二乙基亚硝胺（DEN）启动致癌过程。雄性幼鼠在15日龄时腹腔注射0、2或5 mg / kg DEN。9天后小鼠断奶，并立即给予含有0或0.15%（1500 ppm）I3C的AIN76A半纯化饮食（不含抗氧化剂）。此外，在2个月龄时，一组用2 mg / kg DEN启动的小鼠腹腔注射单剂量（20 mg / kg）的3,4,5,3',4',5'-六氯联苯（HCB），作为促癌阳性对照组。在6或8个月龄时对小鼠的肝脏肿瘤进行采样。每个采样组除HCB组（9只动物）外包含11 - 12只小鼠。8个月后，对于用高剂量DEN启动且喂食I3C的动物，观察到肝癌发生有统计学显著（P < 0.0005）抑制。2个月龄时单次注射HCB显著（P = 0.0003）增强了用2 mg / kg DEN启动的小鼠的肝癌发生。6个月龄采样的组之间没有统计学显著差异。我们的观察结果表明，在婴儿小鼠模型中，饮食中长期给予I3C可抑制DEN启动的肝癌发生。
