Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; Laboratorio de Citogenética y Mutagénesis, IMBICE (CONICET La Plata-UNLP-CICPBA), Universidad Nacional de La Plata, Facultad de Ciencias Naturales y Museo. La Plata, Buenos Aires, Argentina.
Laboratorio de Farmacología de Receptores, ININFA, UBA-CONICET, Argentina.
J Steroid Biochem Mol Biol. 2019 Feb;186:96-104. doi: 10.1016/j.jsbmb.2018.09.021. Epub 2018 Oct 2.
Chlorpyrifos (CPF) is an organophosphorus pesticide used for agricultural pest control all over the world. We have previously demonstrated that environmental concentrations of this pesticide alter mammary gland histological structure and hormonal balance in rats chronically exposed. In this work, we analyzed the effects of CPF on mammary tumors development. Our results demonstrated that CPF increases tumor incidence and reduces latency of NMU-induced mammary tumors. Although no changes were observed in tumor growth rate, we found a reduced steroid hormone receptor expression in the tumors of animals exposed to the pesticide. Moreover, we analyzed the role of epigenetic mechanisms in CPF effects. Our results indicated that CPF alters HDAC1 mRNA expression in mammary gland, although no changes were observed in DNA methylation. In summary, we demonstrate that the exposure to CPF promotes mammary tumors development with a reduced steroid receptors expression. It has also been found that CPF affects HDAC1 mRNA levels in mammary tissue pointing that CPF may act as a breast cancer risk factor.
毒死蜱（CPF）是一种用于世界各地农业害虫防治的有机磷农药。我们之前已经证明，这种农药的环境浓度会改变长期暴露的大鼠的乳腺组织学结构和激素平衡。在这项工作中，我们分析了 CPF 对乳腺肿瘤发展的影响。我们的结果表明 CPF 增加了肿瘤的发生率并降低了 NMU 诱导的乳腺肿瘤的潜伏期。尽管肿瘤生长速度没有变化，但我们发现暴露于农药的动物的肿瘤中类固醇激素受体表达减少。此外，我们分析了表观遗传机制在 CPF 作用中的作用。我们的结果表明 CPF 改变了乳腺组织中 HDAC1 mRNA 的表达，尽管 DNA 甲基化没有变化。总之，我们证明接触 CPF 会促进乳腺肿瘤的发展，并降低类固醇受体的表达。还发现 CPF 影响乳腺组织中 HDAC1 mRNA 水平，表明 CPF 可能是乳腺癌的一个危险因素。
