Rutgers Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, 59 Dudley Rd, New Brunswick, NJ 08901, USA.
Horm Cancer. 2011 Aug;2(4):239-48. doi: 10.1007/s12672-011-0074-6.
Exposure to alcohol during fetal development increases susceptibility to mammary cancer in adult rats. This study determined if early changes in mammary morphology and the insulin-like growth factor (IGF)/estradiol axis are involved in the mechanisms that underlie this increased susceptibility. Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet (pair-fed), or rat chow ad libitum from days 11 to 21 of gestation. At birth, female pups were cross-fostered to ad libitum-fed control dams. Offspring were euthanized at postnatal days (PND) 20, 40, or 80. Animals were injected with BrdU before euthanasia, then mammary glands, serum, and livers were collected. Mammary glands from animals exposed to alcohol in utero displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Mammary IGF-I mRNA was higher in alcohol-exposed animals relative to controls at PND 20, while mammary IGFBP-5 mRNA was lower in this group at PND 40. Hepatic IGF-I mRNA expression was increased at all time points in alcohol-exposed animals, however, circulating IGF-I levels were not altered. These data indicate that alcohol exposure in utero may advance mammary development via the IGF and estradiol systems, which could contribute to increased susceptibility to mammary cancer later in life.
胎儿发育期接触酒精会增加成年大鼠患乳腺癌的易感性。本研究旨在确定乳腺形态和胰岛素样生长因子（IGF）/雌二醇轴的早期变化是否参与了这种易感性增加的机制。妊娠 Sprague-Dawley 大鼠从妊娠第 11 天到 21 天，每天喂食含 6.7%乙醇（酒精）的液体饮食、等热量液体饮食（配对喂养）或自由进食的大鼠饲料。出生时，雌性幼崽被交叉寄养给自由进食的对照母鼠。后代在出生后第 20、40 或 80 天安乐死。安乐死前，动物被注射 BrdU，然后收集乳腺、血清和肝脏。与对照组相比，宫内接触酒精的动物在出生后第 20 和 40 天显示出乳腺上皮细胞增殖和芳香酶表达增加。与对照组相比，酒精暴露组的乳腺 IGF-I mRNA 在出生后第 20 天升高，而在该组中 IGFBP-5 mRNA 在出生后第 40 天降低。酒精暴露组在所有时间点的肝 IGF-I mRNA 表达均增加，然而，循环 IGF-I 水平没有改变。这些数据表明，宫内接触酒精可能通过 IGF 和雌二醇系统促进乳腺发育，从而导致日后患乳腺癌的易感性增加。
