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

HERO ID

2189626

Reference Type

Journal Article

Subtype

Abstract

Year

2008

Language

English

HERO ID 2189626
Material Type Abstract
In Press No
Year 2008
Title Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human prostate epithelial cells
Authors Zhu, Y; Mhaskar, AH; Lehmler, HJ; Robertson, LW; Spitz, DR; Aykin-Burns, N
Journal Free Radical Biology and Medicine
Volume 45
Page Numbers S26-S26
Abstract 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)
Wosid WOS:000260867900065
Url http://www.sciencedirect.com/science/journal/08915849/45/supp/S
Is Certified Translation No
Dupe Override No
Conference Location Indianapolis, IN
Conference Name Society for Free Radical Biology and Medicine 15th Annual Meeting
Conference Date November 19-23, 2008
Is Public Yes
Language Text English
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