Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat
Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat
复制标题
DOI：
10.1093/carcin/19.12.2151
复制
发表时间：
1998-12-01
期刊：
影响因子：
4.7
通讯作者：
Lamartiniere, CA
中科院分区：
文献类型：
--
作者：
Fritz, WA;Coward, L;Lamartiniere, CA
食用大豆含量高的传统饮食的亚洲女性患乳腺癌的几率较低，但当她们移民到美国后，第二代（而不是第一代）失去了这种保护。因此，我们假设早期暴露于染料木素（大豆的主要成分）可能对乳腺癌具有永久性的保护作用，Sprague-Dawley CD大鼠从怀孕到产后第21天暴露于染料木素，浓度为0、25和250 mg /kg AIN-76A饮食。在产后第50天，所有动物均给予80 mg二甲基苯[a]蒽/kg体wt诱导乳腺癌。膳食染料木黄酮对乳腺肿瘤的发展具有剂量依赖性的保护作用（每只大鼠的肿瘤减少）。对整个乳腺的分析表明，21日龄和50日龄的雌性大鼠的末端末端芽较少，末端导管结构未分化，最容易发生癌变。溴脱氧尿苷掺入研究表明，围产期饮食染料木黄酮导致末梢芽增殖室变小。高剂量（250 mg/kg日粮）喂养的大鼠产后7 d血清和乳中染料木素总浓度分别为418 +/- 198和137 pmol/ml。7日龄子代胃乳、血清和乳腺中染料木素总浓度分别为4439 +/- 1109、726 pmol/ml和440 +/- 129 pmol/g。21日龄子代血清和乳腺中染料木素总浓度分别为1810 +/- 135 pmol/ml和370+/-36 pmol/g。围产期饮食中的染料木素对F-0和F-1雌性没有显著的毒性作用。我们得出的结论是，饮食中的染料木素在“生理水平”上增强了细胞分化，导致乳腺细胞的编程，降低了对乳腺癌的易感性，对F-1雌性的生殖道没有观察到毒性。
Asian women consuming a traditional diet high in soy have a low incidence of breast cancer, yet when they emigrate to the USA the second but not the first generation lose this protection. Accordingly, we hypothesized that early exposure to genistein, a major component of soy, could have a permanent protective effect against breast cancer, Sprague-Dawley CD rats were exposed to genistein from conception to day 21 post-partum in the diet at concentrations of 0, 25 and 250 mg genistein/kg AIN-76A diet. At day 50 post-partum, all animals were treated with 80 mg dimethylbenz[a]anthracene/kg body wt to induce mammary cancers. Dietary genistein resulted in dose-dependent protection against development of mammary tumors (fewer tumors per rat). Analysis of mammary whole mounts showed that 21- and 50-day-old female rats had fewer terminal end buds, terminal ductal structures that were undifferentiated and were most susceptible to carcinogenesis. Bromodeoxyuridine incorporation studies revealed that dietary perinatal genistein resulted in a smaller proliferative compartment for terminal end buds. In rats fed the high genistein dose (250 mg/kg diet) total genistein concentrations in the serum and milk of darns 7 days postpartum were 418 +/- 198 and 137 pmol/ml, respectively. Total genistein concentrations in stomach milk, serum and mammary glands of 7-day-old offspring were 4439 +/- 1109 and 726 pmol/ml and 440 +/- 129 pmol/g, respectively. Total genistein concentrations in the serum and mammary glands of 21-day-old offspring were 1810 +/- 135 pmol/ml and 370+/-36 pmol/g, respectively. Dietary perinatal genistein did not cause significant toxicity in F-0 and F-1 females. We conclude that genistein in the diet at 'physiological levels' enhances cell differentiation, resulting in programming of mammary gland cells for reduced susceptibility to mammary cancer, with no observed toxicity to the reproductive tract of F-1 females.