Bisphenol A Increases Mammary Cancer Risk in Two Distinct Mouse Models of Breast Cancer
Bisphenol A Increases Mammary Cancer Risk in Two Distinct Mouse Models of Breast Cancer
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DOI：
10.1095/biolreprod.110.090431
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发表时间：
2011-09-01
影响因子：
3.6
通讯作者：
Keri, Ruth A.
中科院分区：
文献类型：
--
作者：
Lozada, Kristen Weber;Keri, Ruth A.
双酚A（BPA）是一种工业增塑剂，在正常使用过程中会从食品容器中滤出，导致人体暴露。早期和长期暴露于内分泌干扰环境污染物（如BPA）会增加长期健康后果的可能性。我们研究了BPA暴露对乳腺肿瘤易感性的胎儿编程的影响，以及其对体内转化的乳腺癌细胞的生长促进作用。通过对妊娠母鼠的口服管饲，使胎鼠暴露于0、25或250 μ g/kg BPA。后代随后用已知的乳腺致癌物7，12-二甲基苯并[a]蒽（DMBA）处理。虽然没有观察到出生后乳房发育的显著差异，但与溶剂处理的对照组相比，低剂量和高剂量BPA组对DMBA诱导的肿瘤的易感性在统计学上显著增加。为了确定BPA是否也促进已建立的肿瘤生长，将MCF-7人乳腺癌细胞皮下注射到用BPA、17 β-雌二醇或安慰剂单独或与他莫昔芬组合治疗的卵巢切除的NCR nu/nu雌性小鼠的侧腹。雌二醇和BPA治疗组在移植后7周均形成肿瘤，而安慰剂组未检测到肿瘤。他莫昔芬逆转了雌二醇和BPA的作用。我们的结论是，双酚A可能会增加乳腺肿瘤的发生，通过至少两种机制：分子改变胎儿腺体没有相关的形态学变化和直接促进雌激素依赖性肿瘤细胞的生长。这两个结果都表明，在各种生物状态下暴露于BPA会增加小鼠患乳腺癌的风险。
Bisphenol A (BPA) is an industrial plasticizer that leaches from food containers during normal usage, leading to human exposure. Early and chronic exposure to endocrine-disrupting environmental contaminants such as BPA elevates the potential for long-term health consequences. We examined the impact of BPA exposure on fetal programming of mammary tumor susceptibility as well as its growth promoting effects on transformed breast cancer cells in vivo. Fetal mice were exposed to 0, 25, or 250 mu g/kg BPA by oral gavage of pregnant dams. Offspring were subsequently treated with the known mammary carcinogen, 7,12-dimethylbenz[a] anthracene (DMBA). While no significant differences in postnatal mammary development were observed, both low-and high-dose BPA cohorts had a statistically significant increase in susceptibility to DMBA-induced tumors compared to vehicle-treated controls. To determine if BPA also promotes established tumor growth, MCF-7 human breast cancer cells were subcutaneously injected into flanks of ovariectomized NCR nu/nu female mice treated with BPA, 17beta-estradiol, or placebo alone or combined with tamoxifen. Both estradiol-and BPA-treated cohorts formed tumors by 7 wk post-transplantation, while no tumors were detected in the placebo cohort. Tamoxifen reversed the effects of estradiol and BPA. We conclude that BPA may increase mammary tumorigenesis through at least two mechanisms: molecular alteration of fetal glands without associated morphological changes and direct promotion of estrogen-dependent tumor cell growth. Both results indicate that exposure to BPA during various biological states increases the risk of developing mammary cancer in mice.