US EPA

2189626 

Journal Article 

Abstract 

Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human prostate epithelial cells 

Zhu, Y; Mhaskar, AH; Lehmler, HJ; Robertson, LW; Spitz, DR; Aykin-Burns, N 

2008 

Yes 

Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 

45 

S26-S26 

English 

WOS:000260867900065 

http://www.sciencedirect.com/science/journal/08915849/45/supp/S
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is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts

Recent findings suggest that PCBs and PCB metabolites may cause cytotoxicity by inducing oxidative stress and it has been suggested that PCB exposure can increase the risk of developing prostate cancer. in the current study, exponentially growing human prostate epithelial cells (RWPE-1) were exposed in complete serum free KSF medium to PCBs and PCB metabolites (daily concentration of 3 μM) for 5 days. the results from growth curves and clonogenic survival assays showed that PCB153, Aroclor 1254 and the 2-(4-chlorophenyl)-1,2-benzoquinone metabolite of PCB3 (4ClBQ) can induce cell growth suppression and decreased the plating efficiency of RWPE-1 cells, with the 4ClBQ having the most pronounced effects. These same PCBs were also found to increase steady-state levels of intracellular O2•− (as determined by dihydroethidium and MitosoxTMred oxidation) as well as H2O2 (as determined by oxidation of carboxy-2’,7’-dichlorodihydrofluorescein diacetate). Results of confocal microscopy with MitoSOXTMred oxidation coupled with co-localization of Mitotracker green fluorescence in PCB exposed RWPE-1 cells demonstrated the primary localization of increased levels of O2•− was in mitochondria. Finally, treatment with the non-specific thiol antioxidant N-acetyl-cysteine (5 mM, NAC) added 1 hour after the PCB, significantly protected the RWPE-1 cells from the toxicity caused by PCBs and their metabolites. These results clearly support the hypothesis that exposure to PCBs or their metabolites can increase steady-state levels of reactive oxygen species, inhibit cell proliferation, and cause cytotoxicity in exponentially growing human prostate epithelial cells. These data also support the hypothesis that NAC given following PCB intoxication can protect human prostate epithelial cells from cytotoxicity. (Supported by NIEHS P42 ES013661) 

Society for Free Radical Biology and Medicine 15th Annual Meeting 

Indianapolis, IN 

November 19-23, 2008