有机氯暴露与乳腺癌风险

S H Safe, T Zacharewski
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摘要

有机氯工业化合物、燃烧产物和农药在环境中被广泛发现,在鱼类、野生动物、人体组织以及人乳和血清的提取物中也检测到残留。这些化合物中有许多具有性类固醇活性,因此有可能破坏内分泌调节的体内平衡。具有激素活性的有机氯包括:(i)多氯联苯(PCBs)、羟基化多氯联苯、o,p'-滴滴涕和其他具有雌激素受体激动剂活性的有机氯杀虫剂;(ii) p′-DDE,雄激素受体的配体,具有抗雄激素活性;(iii)多氯联苯、2,3,7,8-四氯二苯并对二恶英(TCDD)和与芳烃(Ah)受体结合并表现出组织特异性抗雌激素活性的相关芳烃;和(iv)羟基化的芳香烃结合甲状腺素,甲状腺激素结合蛋白。尽管有研究表明,多氯联苯和DDE的雌激素活性可能是女性患乳腺癌的一个因素,但这些化合物的水平在乳腺癌患者中并没有持续升高,也没有证据表明,在职业上暴露于相对较高水平的多氯联苯或DDE的女性患乳腺癌的几率会增加。相比之下,流行病学研究表明,在意大利Seveso的一次工业事故中暴露于高水平TCDD的妇女,乳腺癌和子宫内膜癌的发病率都有所下降。基于从食物中摄取的激素或从天然化合物中提取的抗激素模拟物,有机氯化合物对雌激素的贡献很小,它们在乳腺癌发展中的作用值得怀疑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Organochlorine exposure and risk for breast cancer.

Organochlorine industrial compounds, combustion products and pesticides have been widely identified in the environment and residues have been detected in extracts prepared from fish, wildlife, human tissues as well as human milk and serum. Many of these compounds possess sex steroid activities and therefore have the potential to disrupt endocrine-regulated homeostasis. Organochlorines which exhibit hormonal activity include: (i) polychlorinated biphenyls (PCBs), hydroxylated PCBs, o,p'-DDT, and other organochlorine insecticides which exhibit estrogen receptor (ER) agonist activities; (ii) p,p'-DDE, a ligand for the androgen receptor which exhibits antiandrogen activity; (iii) PCBs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and related aromatic hydrocarbons which bind the aryl hydrocarbon (Ah) receptor and exhibit tissue-specific antiestrogenic activity; and (iv) hydroxylated aromatics which bind transthyretin, a thyroid hormone binding protein. Although, it has been suggested that the estrogenic activity of PCBs and DDE may be a contributing factor for development of breast cancer in women, levels of these compounds are not consistently elevated in breast cancer patients and there is no evidence that women occupationally-exposed to relatively high levels of PCBs or DDE exhibit an increased incidence of breast cancer. In contrast, epidemiology studies suggest that women exposed to high levels of TCDD during an industrial accident in Seveso, Italy, have a decreased incidence of both breast and endometrial cancer. Based on the dietary intake of hormone or antihormone mimics derived from natural compounds in food, the estrogenic contribution of organochlorine compounds is small and their role in development of breast cancer is questionable.

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