Chronic oral exposure to bisphenol A results in a nonmonotonic dose response in mammary carcinogenesis and metastasis in MMTV-erbB2 mice.
Chronic oral exposure to bisphenol A results in a nonmonotonic dose response in mammary carcinogenesis and metastasis in MMTV-erbB2 mice.
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DOI：
10.1289/ehp.1103850
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发表时间：
2011-11
影响因子：
10.4
通讯作者：
Lamartiniere CA
中科院分区：
文献类型：
--
作者：
Jenkins S;Wang J;Eltoum I;Desmond R;Lamartiniere CA
背景：双酚A（BPA）是一种用于生产塑料和环氧树脂的合成化合物。BPA可以从这些产品中大量浸出，导致人类几乎无处不在的日常暴露。BPA是否对人类有害，特别是当口服与人类相关的浓度时，是一个争论的话题。目的：在这项研究中，我们研究了在成年期慢性口服暴露于BPA对乳腺癌发生的作用，通过使用转基因小鼠模型，自发发展肿瘤，通过过度表达野生型erbB 2 [小鼠乳腺肿瘤病毒（MMTV）-erbB 2]。研究方法：将MMTV-erbB 2小鼠从56日龄至112日龄（用于作用机制）或252日龄（用于肿瘤发生）暴露于0、2.5、25、250或2，500 µg BPA/L饮用水。通过免疫组织化学和免疫印迹法研究了BPA在乳腺中作用的细胞和分子机制。结果：只有低剂量的BPA显著降低肿瘤潜伏期，增加肿瘤多样性，肿瘤负荷和转移的发生率。所有BPA剂量均显著增加细胞增殖指数，但仅较高剂量也增加乳腺中的凋亡指数。在分子水平上，25 µg BPA/L，而不是2，500 µg BPA/L，增加乳腺中erbB 2，erbB 3，胰岛素样生长因子1受体和Akt的磷酸化。讨论：低，但不是高，BPA剂量显着加速乳腺肿瘤的发生和转移的MMTV-erbB 2小鼠。细胞增殖和凋亡指数的组合比率以及蛋白质表达的改变最好地预测了每个剂量的BPA改变该模型中肿瘤发生的能力。
Background: Bisphenol A (BPA) is a synthetic compound used to produce plastics and epoxy resins. BPA can leach from these products in appreciable amounts, resulting in nearly ubiquitous daily exposure to humans. Whether BPA is harmful to humans, especially when administered orally in concentrations relevant to humans, is a topic of debate. Objectives: In this study, we investigated the role of chronic oral exposure to BPA during adulthood on mammary carcinogenesis by using a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type erbB2 [mouse mammary tumor virus (MMTV)-erbB2]. Methods: MMTV-erbB2 mice were exposed to 0, 2.5, 25, 250, or 2,500 µg BPA/L drinking water from 56 until 112 days of age (for mechanism of action) or 252 days of age (for tumorigenesis). Cellular and molecular mechanisms of BPA action in the mammary gland were investigated via immunohistochemistry and immunoblotting. Results: Only low doses of BPA significantly decreased tumor latency and increased tumor multiplicity, tumor burden, and the incidence of metastasis. All BPA doses significantly increased the cell proliferation index, but only the higher doses also increased the apoptotic index in the mammary gland. At the molecular level, 25 µg BPA/L, but not 2,500 µg BPA/L, increased phosphorylation of erbB2, erbB3, insulin-like growth factor 1 receptor, and Akt in the mammary gland. Discussion: Low, but not high, BPA doses significantly accelerated mammary tumorigenesis and metastasis in MMTV-erbB2 mice. The combined ratio of cell proliferation and apoptosis indices and alterations in protein expression best predicted the ability of each dose of BPA to alter tumorigenesis in this model.
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影响因子：
4.8
作者：
Kuiper, GGJM;Lemmen, JG;Gustafsson, JÄ
通讯作者：
Gustafsson, JÄ
DOI：
10.1080/02652030210134236
发表时间：
2003-07-01
期刊：
FOOD ADDITIVES AND CONTAMINANTS
影响因子：
--
作者：
Brede, C;Fjeldal, P;Herikstad, H
通讯作者：
Herikstad, H
影响因子：
3.5
作者：
Jones, Laundette P.;Sampson, Aishia;Kang, Hyo Jin;Kim, Hee Jeong;Yi, Yong-Weon;Kwon, Sun Young;Babus, Janice K.;Wang, Antai;Bae, Insoo
通讯作者：
Bae, Insoo
DOI：
10.2131/jts.26.111
发表时间：
2001-08-01
期刊：
The Journal of toxicological sciences
影响因子：
--
作者：
Kim, H S;Han, S Y;Park, K L
通讯作者：
Park, K L
影响因子：
10.4
作者：
Calafat AM;Kuklenyik Z;Reidy JA;Caudill SP;Ekong J;Needham LL
通讯作者：
Needham LL