Division of Cancer Prevention, National Cancer Institute, Executive Plaza North, Suite 2110, NIH, NCI, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Oncol Rep. 2011 Sep;26(3):731-6. doi: 10.3892/or.2011.1316. Epub 2011 May 23.
The abilities of 5,6-benzoflavone (5,6-BF, a synthetic flavonoid), indole-3-carbinol (I3C, a plant derived product) or diindolylmethane (DIM, a condensation product of I3C) to alter the induction of mammary cancers induced by the carcinogens 7,12-dimethylbenzanthracene (DMBA) or N-methyl-N-nitrosourea (MNU) were evaluated. Interestingly, the first two agents act as aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DMBA-induced mammary carcinogenesis. Agents were administered for 14 days starting 7 days prior to a single dose of the carcinogen. Evaluated over an extensive range of doses (165, 550 and 1650 ppm in the diet), 5,6-BF caused a dose-dependent decrease of mammary cancers. In addition, 5,6-BF at doses of 1650 and 165 ppm in the diet blocked the induction of DMBA-induced DNA adducts in the mammary gland by approximately 85% and 45%, respectively. In contrast, DIM (180 or 20 mg/kg BW/day) failed to block induction of DMBA tumors. The effect of these agents on the promotion/progression phase of carcinogenesis using the MNU mammary cancer model was also determined. 5,6-BF (1650 or 165 ppm in the diet), I3C (180 or 60 mg/kg BW/day administered by gavage), or DIM (180 or 60 mg/kg BW/day by gavage) were initiated 5 days after the administration of MNU, and continually thereafter. 5,6-BF decreased MNU- induced mammary tumor multiplicity by 40-60%. I3C reduced tumor multiplicity at the high dose, while DIM at either dose had minimal effects on tumor multiplicity. Thus, 5,6-BF and I3C were highly effective against initiation of DMBA-induced mammary carcinogenesis, and were also effective against MNU-induced tumors during the promotion/progression phase of carcinogenesis. In contrast, DIM had minimal effects in either model; arguing that administration of DIM is not analogous to administration of I3C.
评估了 5,6-苯并黄酮（5,6-BF，一种合成黄酮类化合物）、吲哚-3-甲醇（I3C，一种植物衍生产品）或二吲哚基甲烷（DIM，I3C 的缩合产物）改变致癌剂 7,12-二甲基苯并蒽（DMBA）或 N-甲基-N-亚硝脲（MNU）诱导的乳腺癌发生的能力。有趣的是，前两种试剂作为芳基烃受体（AhR）激动剂，而 DIM 则不是。最初，这些试剂被检查是否能够抑制 DMBA 诱导的乳腺癌发生。试剂在致癌物单次给药前 7 天开始连续 14 天给药。在广泛的剂量范围内（饮食中 165、550 和 1650ppm）评估时，5,6-BF 引起乳腺肿瘤的剂量依赖性减少。此外，饮食中 5,6-BF 的剂量为 1650 和 165ppm 时，分别约 85%和 45%阻断 DMBA 诱导的乳腺 DNA 加合物的诱导。相比之下，DIM（180 或 20mg/kgBW/天）未能阻断 DMBA 肿瘤的诱导。还确定了这些试剂对使用 MNU 乳腺癌模型的致癌作用的促进/进展阶段的影响。5,6-BF（饮食中 1650 或 165ppm）、I3C（灌胃给予 180 或 60mg/kgBW/天）或 DIM（灌胃给予 180 或 60mg/kgBW/天）在 MNU 给药后 5 天开始，并持续给药。5,6-BF 使 MNU 诱导的乳腺肿瘤多发性降低 40-60%。I3C 降低了高剂量时的肿瘤多发性，而 DIM 以任何剂量对肿瘤多发性的影响都很小。因此，5,6-BF 和 I3C 对 DMBA 诱导的乳腺癌发生的起始具有高度的抑制作用，并且在致癌作用的促进/进展阶段对 MNU 诱导的肿瘤也有效。相比之下，DIM 在两种模型中均具有最小的影响；这表明给予 DIM 与给予 I3C 并不相似。
