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有机磷农药与乳腺癌进展

Organophosphorous pesticides in breast cancer progression.

作者信息

Cabello G, Juarranz A, Botella L M, Calaf G M

机构信息

Research Center for the Man in the Desert, University of Tarapaca, Arica, Chile.

出版信息

J Submicrosc Cytol Pathol. 2003 Jan;35(1):1-9.

Abstract

Environmental substances may be involved in the etiology of breast cancers. Many studies have found an association between cancer in humans and exposure to agricultural pesticides. Organophosphorous pesticides have been used to control mosquito plagues. Parathion and malathion, organophosphorous pesticides are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Their primary target of action in insects is the nervous system whereby they inhibit the enzyme acetylcholinesterase at synaptic junction. Atropine is a parasympatholytic alkaloid used as an antidote to acetylcholinesterase inhibitors. We have established an experimental breast cancer model, where epithelial cells in the rat mammary gland underwent a stepwise transformation into malignant cells by exposure to pesticides (Cabello et al, 2001). The aim of this work was to examine whether pesticides were able to induce progression of malignant transformation of a human breast epithelial cell line, MCF7. These results showed that parathion and malathion increased PCNA and induced mutant p53 protein expression of MCF7 cells in comparison to controls and atropine inhibited such action. These results indicated that organophosphorous pesticides can induce more changes in this malignant breast cell line, inducing another step in the progression of the transformation process and atropine on the other hand inhibited the effect of such substances.

摘要

环境物质可能与乳腺癌的病因有关。许多研究发现人类癌症与接触农用杀虫剂之间存在关联。有机磷杀虫剂已被用于控制蚊虫灾害。对硫磷和马拉硫磷这两种有机磷杀虫剂是胆碱酯酶抑制剂,负责水解体内的胆碱酯,包括胆碱能突触处的乙酰胆碱。它们在昆虫体内的主要作用靶点是神经系统,在突触连接处抑制乙酰胆碱酯酶。阿托品是一种抗胆碱能生物碱,用作乙酰胆碱酯酶抑制剂的解毒剂。我们建立了一个实验性乳腺癌模型,通过接触杀虫剂,大鼠乳腺上皮细胞逐步转化为恶性细胞(卡贝洛等人,2001年)。这项工作的目的是研究杀虫剂是否能够诱导人乳腺上皮细胞系MCF7的恶性转化进程。这些结果表明,与对照组相比,对硫磷和马拉硫磷增加了MCF7细胞的增殖细胞核抗原(PCNA)并诱导了突变型p53蛋白表达,而阿托品抑制了这种作用。这些结果表明,有机磷杀虫剂可在这种恶性乳腺细胞系中诱导更多变化,在转化过程的进程中引发又一步变化,而阿托品则抑制了此类物质的作用。

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