Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol.
Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol.
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发表时间：
1995-05
影响因子：
2
通讯作者：
C. Grubbs;V. Steele;T. Casebolt;M. Juliana;I. Eto;Whitaker Lm;K. Dragnev;G. Kelloff;Lubet Rl
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文献类型：
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作者：
C. Grubbs;V. Steele;T. Casebolt;M. Juliana;I. Eto;Whitaker Lm;K. Dragnev;G. Kelloff;Lubet Rl
使用三种不同的方案评估了十字花科蔬菜的一种成分吲哚-3-甲醇在预防化学诱发的乳腺肿瘤方面的功效。由于这种化合物不稳定，因此通过管饲而不是在饮食中给药。初步剂量范围研究表明，100 和 50 毫克/天、每周 5 次的剂量水平对雌性 Sprague-Dawley 大鼠没有毒性。 DMBA 模型的初步研究表明，在起始和促进阶段施用吲哚-3-甲醇是高效的化学预防方法（癌症多重性降低 91-96%）。随后的研究表明，仅在起始阶段（DMBA 前 7 天至 DMBA 后 7 天）施用 3-吲哚甲醇作为化学预防剂也是非常有效的。长期用吲哚-3-甲醇治疗的动物肝脏中酶水平的测定显示各种 I 期和 II 期药物代谢酶的诱导水平很高。最后，在 MNU（一种直接作用致癌物）之前和之后施用吲哚-3-甲醇可导致乳腺肿瘤多样性显着降低 (65%)。这些结果支持了先前的研究，即吲哚-3-甲醇可以通过直接和间接作用的致癌物质预防乳腺癌的发生。因此，3-吲哚甲醇可能是女性乳腺癌化学预防的良好候选药物。
Indole-3-carbinol, a component of cruciferous vegetables, was evaluated for it efficacy in the prevention of chemically-induced mammary tumors using three different protocols. Because this compound was unstable, it was administered by gavage rather than in the diet. A preliminary dose range study revealed that dose levels of 100 and 50 mg/day, 5x/week, were not toxic to female Sprague-Dawley rats. Initial studies in the DMBA model showed that administering indole-3-carbinol during the initiation and promotion phases were highly effective chemopreventive methods (91-96% reduction in cancer multiplicity). Subsequent studies showed that the administration of indole-3-carbinol only during the initiation phase (7 days prior to until 7 days post DMBA) was also highly effective as a chemopreventive agent. Determination of enzyme levels in the livers of animals treated long-term with indole-3-carbinol showed high levels of induction of various phase I and phase II drug metabolizing enzymes. Finally, indole-3-carbinol when administered both prior to and after MNU (a direct acting carcinogen) caused a significant decrease (65%) in mammary tumor multiplicity. These results support previous studies that indole-3-carbinol can prevent mammary carcinogenesis by direct and indirect acting carcinogens. Therefore, indole-3-carbinol might be a good candidate for chemoprevention of breast cancer in women.