Microdoses Levels of Butadiene Diepoxide (BDO<sub>2</sub>) Induced Toxicity in Prostate Cancer Cells

Abstract

Low-level exposure to environmental pollutants such as BDO 2 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 (BDO 2 ) in prostate cancer cells. We observed that micro-doses of BDO 2 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 BDO 2 toxicity which was reversed by transient transfection of AR into theses cell. Exposure of prostate cells to BDO 2 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 BDO 2 , but BDO 2 -induced apoptotic protein expression was unaltered. This study provides evidence that micro-doses of BDO 2 modulate prostate cell toxicity by promoting apoptosis and tumor gene expression.