This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator. 1,3-butadine (1,3-BD) has received attention due to its classification by the EPA as a potential reproductive carcinogen. Both animal and population studies support the reproductive carcinogenicity of 1,3-BD and its metabolites. However, the direct effects of 1,3-BD on reproductive tissue or in cell culture have not been fully investigated. This report investigated whether 1,3-BD's toxicity in prostate cell requires the presence of a functional androgen receptor. The androgen receptor (AR) positive LNCaP and AR negative DU145 cell lines were subjected to increasing concentration of BDO2 (0.0 nM to100nM) for different period ranging from 6,12 or 24h. The effect of BDO was evaluated by measuring cellular cytotoxicity by MTT assay, morphological sign of apoptosis using Fluorescent microscopy, prostate cell integrity using PSA secretion and gene expression of apoptotic proteins using QRT-PCR and Western blot analysis. The AR negative DU145 cells were more sensitive to BDO2 toxicity as compared to the AR positive LNCaP cells. As expected there was no notable change in prostate cell integrity was measure by PSA secretion. QRT-PCR and Western blot analysis indicates that the levels of apoptotic proteins expression were decrease in AR positive LNCaP cells. Transient transfection of an functional AR into the AR negative DU145 cells did not alter BDO2 induce apoptotic protein expression but reverse the expression patter for certain AR dependent gene expression. Our result indicate that AR status may determine the toxicity of 1,3-BD and its metabolites in prostate cells.
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