Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats.
Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats.
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在大鼠中，围产期给予双足A作为潜在的乳腺癌。
DOI：
10.1289/ehp.1306734
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发表时间：
2013-09
影响因子：
10.4
通讯作者：
Soto AM
中科院分区：
文献类型：
--
作者：
Acevedo N;Davis B;Schaeberle CM;Sonnenschein C;Soto AM
背景：环境中双酚A（BPA）暴露会影响啮齿类和灵长类动物的乳腺发育。出生前暴露于环境相关剂量的BPA增加了50天的Wistar-Furth大鼠导管内增生和导管原位癌的数量。目标：我们的目的是确定母鼠仅在妊娠期或整个哺乳期暴露于BPA是否会影响雌性后代乳腺肿瘤的发病率。研究方法：我们从妊娠第9天（GD）至出生以及从GD 9至出生后第21天（PND），以0、0.25、2.5、25或250 μg BPA/kg BW/天的剂量对妊娠Sprague-Dawley大鼠进行处理。在四个时间点检查BPA暴露后代的乳腺癌前病变和肿瘤病变。为了评估循环BPA水平，我们仅在妊娠期间或在妊娠/哺乳期间将妊娠大鼠暴露于溶剂或250 μg BPA/kg BW/天，并分析了来自母鼠、胎儿和哺乳幼崽的血清中的总BPA和未结合BPA。结果：在暴露于250 μg BPA/kg BW/天的母鼠和胎鼠以及33%的幼鼠血清中检测到总BPA和未结合BPA。暴露的母鼠和胎儿（妊娠期）以及暴露的母鼠和幼崽（妊娠期/哺乳期）中的未结合BPA水平在人类中发现的水平范围内。早在PND 50时，所有剂量组中BPA暴露雌性后代均出现肿瘤前病变。出乎意料的是，到PND 90时，BPA暴露后代中出现乳腺腺癌。结论：我们的研究结果表明，在没有任何额外的致癌治疗的情况下，在妊娠期和哺乳期发育暴露于环境相关水平的BPA诱导乳腺肿瘤。因此，BPA可能是一种完全的乳腺致癌物。引文：阿切韦多N，戴维斯B，Schaeberle CM，Sonnenschein C，索托AM. 2013.围产期给药双酚A作为大鼠乳腺致癌物。环境健康展望121：1040-1046; http://dx.doi.org/10.1289/ehp.1306734
Background: Environmental exposure to bisphenol A (BPA) affects mammary gland development in rodents and primates. Prenatal exposure to environmentally relevant doses of BPA increased the number of intraductal hyperplasias and ductal carcinomas in situ by 50 days of age in Wistar-Furth rats. Objective: We aimed to determine whether BPA exposure of dams during gestation only or throughout lactation affects the incidence of mammary gland neoplasia in female offspring. Methods: We treated pregnant Sprague-Dawley rats with BPA at 0, 0.25, 2.5, 25, or 250 μg BPA/kg BW/day from gestational day (GD) 9 to birth and from GD9 to postnatal day (PND) 21. Mammary glands from BPA-exposed offspring were examined at four time points for preneoplastic and neoplastic lesions. To assess circulating BPA levels, we exposed pregnant rats to vehicle or 250 μg BPA/kg BW/day during gestation only or during gestation/lactation and analyzed sera from dams, fetuses, and nursing pups for total and unconjugated BPA. Results: Total and unconjugated BPA were detected in sera from 100% of dams and fetuses and 33% of pups exposed to 250 μg BPA/kg BW/day. Unconjugated BPA levels in exposed dams and fetuses (gestational) and in exposed dams and pups (gestational/lactational) were within levels found in humans. Preneoplastic lesions developed in BPA-exposed female offspring across all doses as early as PND50. Unexpectedly, mammary gland adenocarcinomas developed in BPA-exposed offspring by PND90. Conclusions: Our findings suggest that developmental exposure to environmentally relevant levels of BPA during gestation and lactation induces mammary gland neoplasms in the absence of any additional carcinogenic treatment. Thus, BPA may act as a complete mammary gland carcinogen. Citation: Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM. 2013. Perinatally administered bisphenol A acts as a mammary gland carcinogen in rats. Environ Health Perspect 121:1040–1046; http://dx.doi.org/10.1289/ehp.1306734
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