Murrill W B, Brown N M, Zhang J X, Manzolillo P A, Barnes S, Lamartiniere C A
Department of Pharmacology and Toxicology, University of Alabama at Birmingham 35294-0019, USA.
Carcinogenesis. 1996 Jul;17(7):1451-7. doi: 10.1093/carcin/17.7.1451.
Genistein, a component of soy, was administered to prepubertal female Sprague-Dawley CD rats and investigated for chemoprevention against mammary cancer. Genistein, at 500 microgram/g body wt or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO), was injected (s.c.) on days 16, 18 and 20 post-partum. At day 50 post-partum all animals were exposed to 80 microgram dimethylbenz[a]anthracene (DMBA) per g body wt. Animals treated prepubertally with genistein as compared to DMSO had reduced incidence and significantly fewer adenocarcinomas per animal. Mammary whole mount analysis showed that prepubertal genistein treatment resulted in mammary glands of 50-day-old rats developing fewer terminal end buds and more lobules II. Cell proliferation studies with bromodeoxyuridine (BrdU) showed that terminal end buds from mammary glands of 50-day-old females treated prepubertally with genistein had significantly fewer cells in S-phase of the cell cycle. Serum genistein concentrations in 21- and 50-day-old females following prepubertal genistein treatment were 4.2 +/- 0.6 micromol and 102 +/- 30 nM, respectively. Animals treated prepubertally with genistein as compared to vehicle spent more time in the estrus phase of the estrus cycle, although all animals did cycle. In 50-day-old females, circulating estradiol-17 beta and progesterone concentrations were not significantly altered by the prepubertal genistein treatment. Oocyte/follicle counts and numbers of atretic follicles and corpora lutea were not significantly different between the genistein- and vehicle-treated animals. We conclude that genistein treatment during the prepubertal period can suppress the development of chemically-induced mammary cancer without significant toxicity to the endocrine/reproductive system.
染料木黄酮是大豆的一种成分，将其给予青春期前的雌性斯普拉格 - 道利CD大鼠，并研究其对乳腺癌的化学预防作用。在产后第16、18和20天，以500微克/克体重的染料木黄酮或等量体积的溶媒二甲基亚砜（DMSO）进行皮下注射。在产后第50天，所有动物均接受每克体重80微克的二甲基苯并[a]蒽（DMBA）处理。与DMSO处理的动物相比，青春期前用染料木黄酮处理的动物发病率降低，每只动物的腺癌数量显著减少。乳腺整体分析表明，青春期前用染料木黄酮处理导致50日龄大鼠的乳腺发育出更少的终末芽和更多的II型小叶。用溴脱氧尿苷（BrdU）进行的细胞增殖研究表明，青春期前用染料木黄酮处理的50日龄雌性大鼠乳腺的终末芽在细胞周期的S期的细胞数量显著减少。青春期前用染料木黄酮处理后，21日龄和50日龄雌性大鼠血清中的染料木黄酮浓度分别为4.2±0.6微摩尔和102±30纳摩尔。与溶媒处理的动物相比，青春期前用染料木黄酮处理的动物在发情周期的发情期花费的时间更多，尽管所有动物都有发情周期。在50日龄雌性大鼠中，青春期前用染料木黄酮处理并未显著改变循环中的雌二醇 - 17β和孕酮浓度。染料木黄酮处理组和溶媒处理组动物的卵母细胞/卵泡计数、闭锁卵泡数量和黄体数量没有显著差异。我们得出结论，青春期前给予染料木黄酮可抑制化学诱导的乳腺癌的发展，且对内分泌/生殖系统无明显毒性。
