GENISTEIN SUPPRESSES MAMMARY-CANCER IN RATS

GENISTEIN SUPPRESSES MAMMARY-CANCER IN RATS
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DOI:
10.1093/carcin/16.11.2833
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发表时间:
1995-11-01
期刊:
影响因子:
4.7
通讯作者:
BARNES, S
BARNES, S
中科院分区:
医学2区
文献类型:
--
作者:
LAMARTINIERE, CA;MOORE, JB;BARNES, S

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雌性sd大鼠分别于产后2、4、6天注射5 mg染料木素(一种大豆植物雌激素)或20 μ l二甲基亚砜(DMSO),第50天注射80 μ g二甲基苯[a]蒽(DMBA)/g体重。与DMSO相比,接受染料木素治疗的新生动物潜伏期增加,DMBA诱导的乳腺腺癌发病率和多样性降低。乳腺全载分析显示,50日龄雌性大鼠经染料木素处理后,终芽数量减少,细胞增殖研究显示,50日龄雌性大鼠经染料木素处理后,终芽、终导管、I小叶和II小叶中处于细胞周期s期的细胞百分比和总数均较对照组低,阴道口出现时间较对照组早。50日龄雌鼠经染料木黄酮处理后,出现腔内卵泡闭闭、黄体减少、循环孕酮降低,但雌二醇-17 β浓度未见下降;21日龄新生大鼠乳腺增大,终末芽和终末导管增多,终末导管结构增殖活性增强;新生儿染料木素治疗似乎通过直接作用于末端导管结构的成熟和改变内分泌系统以减少乳腺细胞增殖来发挥其化学预防作用。
Female Sprague-Dawley CD rats were injected s.c. with 5 mg genistein, a soy phytoestrogen, or 20 mu l of the vehicle, dimethylsulfoxide (DMSO), on days 2, 4 and 6 postpartum, At day 50, they were exposed to 80 mu g dimethylbenz[a]anthracene (DMBA)/g body wt. Animals treated neonatally with genistein as compared to DMSO had increased latency and reduced incidence and multiplicity of DMBA-induced mammary adenocarcinomas. Mammary whole mount analysis showed that 50 day old female rats treated neonatally with genistein had fewer terminal end buds, Cell proliferation studies revealed that 50 day old genistein-treated rats had lower percentages and total numbers of cells in the S-phase of the cell cycle in terminal end buds, terminal ducts, lobules I and lobules II, In genistein-treated as compared to vehicle-treated female rats, vaginal openings occurred earlier, the estrus cycle was disrupted and the uterine-ovarian weights were smaller, In 50 day old genistein-treated females there were atretic antral follicles, fewer corpora lutea, and lower circulating progesterone but not estradiol-17 beta concentrations, In 21 day old rats treated neonatally with genistein, mammary glands were larger and there were more terminal end buds and terminal ducts, and more proliferative activity in all terminal ductal structures, It appears that neonatal genistein-treatment exerted its chemoprevention action by acting directly to enhance maturation of terminal ductal structures and by altering the endocrine system to reduce cell proliferation in the mammary gland.