A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition
A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition
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DOI：
10.2307/3454705
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发表时间：
2001-05-01
影响因子：
10.4
通讯作者：
Calaf, G
中科院分区：
文献类型：
--
作者：
Cabello, G;Valenzuela, M;Calaf, G
环境化学物质可能与乳腺癌的病因有关。许多研究都探讨了人类癌症与农业农药暴露之间的关系。有机磷杀虫剂已广泛用于控制蚊患。对硫磷和马拉硫磷是有机磷农药，广泛用于控制大田作物、水果和蔬菜的各种吸吮和咀嚼害虫。它们与天然存在的化合物有许多结构相似之处，它们在昆虫中的主要作用靶点是神经系统;它们抑制突触连接处乙酰胆碱酯酶的释放。乙丝氨酸、马拉硫磷和马拉硫磷是胆碱酯酶抑制剂，负责体内胆碱酯的水解，包括胆碱能突触处的乙酰胆碱。阿托品是一种副交感神经毒性生物碱，被用作乙酰胆碱酯酶抑制剂的解毒剂。本研究的目的是研究农药是否能够诱导大鼠乳腺的恶性转化，并确定这些物质诱导的改变是否会增加影响这种转化的胆碱能激活。这些结果表明，在约28个月后，依赛福、依赛福和马拉硫磷分别增加了44日龄大鼠乳腺末端芽的细胞增殖，随后分别形成了8.6%、14.3%和24.3%的乳腺癌。与此同时，这些动物血清中的乙酰胆碱酯酶活性从对照组的9.78 +/- 0.78 U/mL分别降至依地孕酮、依地孕酮和马拉硫磷给药组的3.05 +/- 0.06 U/mL、2.57 +/- 0.15 U/mL和3.88 +/- 0.44 U/mL。然而，阿托品单独诱导了显著的（p < 0.05）乙酰胆碱酯酶活性从对照值9.78 +/- 0.78降低到单独阿托品的4.38 +/- 0.10，降低到阿托品与依地平组合的1.32 +/- 0.06，以及阿托品与马拉硫磷的2.39 +/- 0.23，无乳腺肿瘤形成。这些结果表明，有机磷农药引起的变化，影响乳腺上皮细胞的致癌过程中，这种变化发生在神经系统的水平，通过增加胆碱能刺激。
Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and agricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Eserine, parathion, and malathion are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Atropine, a parasympatholytic alkaloid, is used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the cholinergic activation influencing such transformation. These results showed that eserine, parathion, and malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary carcinomas, respectively, after about 28 months. At the same time, acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the eserine-, parathion-, and malathion-treated groups, respectively. However, atropine alone induced a significant (p < 0.05) decrease in the acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for atropine alone, to 1.32 +/- 0.06 for atropine in combination with eserine, and 2.39 +/- 0.23 for atropine with malathion, and there was no mammary tumor formation. These results indicate that organophosphorous pesticides induce changes in the epithelium of mammary gland influencing the process of carcinogenesis, and such alterations occur at the level of nervous system by increasing the cholinergic stimulation.