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Microdoses Levels of Butadiene Diepoxide (BDO2) Induced Toxicity in Prostate Cancer Cells

机译:微剂量水平的丁二烯二环氧化物(BDO2)在前列腺癌细胞中诱导的毒性

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Low-level exposure to environmental pollutants such as BDO2 contributes directly and indirectly to an increase in PCa. The aim of this study was to define the cellular changes associated with micro-doses of Butadiene Diepoxide (BDO2) in prostate cancer cells. We observed that micro-doses of BDO2 resulted in dose- and time-dependent increases in cytotoxicity and increased expression of prostate tumor markers in LNCaP(AR+) and DU145(AR-) cells. There was an increased sensitivity of DU145(AR-) cells to BDO2 toxicity which was reversed by transient transfection of AR into theses cell. Exposure of prostate cells to BDO2 increases cytotoxicity, and apoptosis, which correlates with increases in caspases and Bcl2 protein and mRNA levels. In cell DU145(AR-) cell transient transfected with a functional AR, the levels of cytotoxicity and caspase activity were decreased in the presence of BDO2, but BDO2-induced apoptotic protein expression was unaltered. This study provides evidence that micro-doses of BDO2 modulate prostate cell toxicity by promoting apoptosis and tumor gene expression.
机译:低水平暴露于环境污染物(如BDO2)直接或间接地导致PCa的增加。这项研究的目的是确定与前列腺癌细胞中的丁二烯二环氧化物(BDO2)微剂量相关的细胞变化。我们观察到微剂量的BDO2导致LNCaP(AR +)和DU145(AR-)细胞中细胞毒性的剂量和时间依赖性增加以及前列腺肿瘤标记物的表达增加。 DU145(AR-)细胞对BDO2毒性的敏感性增加,这可以通过将AR瞬时转染到这些细胞中来逆转。前列腺细胞暴露于BDO2会增加细胞毒性和凋亡,这与胱冬蛋白酶和Bcl2蛋白质和mRNA水平的增加有关。在功能性AR转染的DU145(AR-)细胞中,在存在BDO2的情况下细胞毒性和半胱天冬酶活性水平降低,但BDO2诱导的凋亡蛋白表达未改变。这项研究提供的证据表明,微剂量的BDO2通过促进凋亡和肿瘤基因表达来调节前列腺细胞毒性。

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