Safe S H, Zacharewski T
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.
Prog Clin Biol Res. 1997;396:133-45.
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.
有机氯工业化合物、燃烧产物及农药在环境中已被广泛识别,并且在从鱼类、野生动物、人体组织以及人乳和血清中提取的物质中检测到了残留。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。表现出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'-滴滴涕以及其他表现出雌激素受体(ER)激动剂活性的有机氯杀虫剂;(ii)p,p'-二氯二苯二氯乙烯(p,p'-DDE),一种雄激素受体配体,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)以及与芳烃(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;(iv)与甲状腺素结合蛋白转甲状腺素蛋白结合的羟基化芳烃。尽管有人认为多氯联苯和p,p'-DDE的雌激素活性可能是女性患乳腺癌的一个促成因素,但这些化合物的水平在乳腺癌患者中并非持续升高,而且没有证据表明职业性接触相对高水平多氯联苯或p,p'-DDE的女性患乳腺癌的发病率增加。相比之下,流行病学研究表明,在意大利塞韦索的一次工业事故中接触高浓度TCDD的女性,乳腺癌和子宫内膜癌的发病率均有所降低。基于从食物中的天然化合物衍生而来的激素或抗激素模拟物的膳食摄入量,有机氯化合物的雌激素贡献很小,它们在乳腺癌发生中的作用值得怀疑。