A New Player in Environmentally Induced Oxidative Stress: Polychlorinated Biphenyl Congener, 3,3'-Dichlorobiphenyl (PCB11)
Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa 52242, USA.Toxicological Sciences (Impact Factor: 3.85). 08/2013; 136(1). DOI: 10.1093/toxsci/kft186
Recent analysis of air samples from Chicago and Lake Michigan areas observed a ubiquitous airborne PCB congener, 3,3'-dichlorobiphenyl (PCB 11). Our analysis of serum samples also revealed the existence of hydroxylated metabolites of PCB11 in human blood. Because, PCBs and PCB metabolites have been suggested to induce oxidative stress, this study sought to determine whether environmental exposure to PCB11 and its 4-hydroxyl metabolite could induce alterations in steady-state levels of reactive oxygen species (ROS) and cytotoxicity in immortalized human prostate epithelial cells (RWPE-1). This study also examines if antioxidants could protect the cells from PCB11 induced cytotoxicity. Exponentially growing RWPE-1 cells were exposed to 3 μM PCB 11 and its metabolite, 3,3'-dichlorobiphenyl-4-ol (4-OH-PCB11) as well as an airborne PCB mixture resembling the Chicago ambient air congener profile, everyday for 5 days. Results showed that 4-OH-PCB11 could significantly induce cell growth suppression and decrease the viability and plating efficiency of RWPE-1 cells. 4-OH-PCB11 also significantly increased steady-state levels of intracellular O2(•) as well as hydroperoxides. Finally, treatment with the combination of polyethylene glycol conjugated CuZnSOD and catalase added 1 hour after 4-OH-PCB11 exposures, significantly protected RWPE-1 cells from PCB toxicity.The results strongly support the hypothesis that exposure to a hydroxylated metabolite of PCB11 can inhibit cell proliferation and cause cytotoxicity by increasing steady state levels of ROS. Furthermore, antioxidant treatments following PCBs exposure could significantly mitigate the PCB-induced cytotoxicity in exponentially growing human prostate epithelial cells.
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- "Several studies have reported that some PCBs and their metabolites alter cellular glutathione homeostasis, and that NAC co-treatment can attenuate adverse effects in cells in culture and in vivo following PCB exposure (Lai et al. 2010; Slim et al. 2000; Srinivasan et al. 2001; Zhu et al. 2013). "
ABSTRACT: Chiral polychlorinated biphenyl (PCB) congeners, such as PCB 136, are atropselectively metabolized to various hydroxylated PCB metabolites (HO-PCBs). The present study investigates the effect of two thiol antioxidants, glutathione and N-acetyl-cysteine (NAC), on profiles and chiral signatures of PCB 136 and its HO-PCB metabolites in rat liver microsomal incubations. Liver microsomes prepared from rats pretreated with phenobarbital were incubated with PCB 136 (5 μM) in the presence of the respective antioxidant (0-10 mM), and levels and chiral signatures of PCB 136 and its HO-PCB metabolites were determined. Three metabolites, 5-136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol), 4-136 (2,2',3,3',6,6'-hexachlorobiphenyl-4-ol), and 4,5-136 (2,2',3,3',6,6'-hexachlorobiphenyl-4,5-diol), were detected in all incubations, with 5-136 being the major metabolite. Compared to microsomal incubations without antioxidant, levels of 4,5-136 increased with increasing antioxidant concentration, whereas levels of PCB 136 and both mono-HO-PCBs were not affected by the presence of either antioxidant. PCB 136, 4-136, and 5-136 displayed significant atropisomeric enrichment; however, the direction and extent of the atropisomeric enrichment was not altered in the presence of an antioxidant. Because 4,5-136 can either be conjugated to a sulfate or glucuronide metabolite that is readily excreted or further oxidized a potentially toxic PCB 136 quinone, the effect of both thiol antioxidants on 4,5-136 formation suggests that disruptions of glutathione homeostasis may alter the balance between both metabolic pathways and, thus, PCB 136 toxicity in vivo.
- "Despite this knowledge, human uptake, metabolism, and toxic response to PCB 11 and other nonlegacy PCBs remains poorly understood. Initial laboratory studies with animals and plants have demonstrated the potential of PCB 11 to become bioavailable to humans through inhalation and to be accessible for biotransformation (Hu et al. 2010b, 2013, 2012, Hu et al. 2014, Zhu et al. 2013). In 2013, PCB 11 was reportedly detected in human serum for the fi rst time, thereby further emphasizing the need for a better understanding of the exposure , metabolism, and toxicities of nonlegacy PCBs (Marek et al. 2013b). "
Article: Regulation of PCBs
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ABSTRACT: The non-Aroclor congener 3,3'-dichlorobiphenyl (PCB 11) has been recently detected in air, water, sediment, and biota. It has been known since at least the 1970s that this congener is produced inadvertently during the production of certain organic pigments. PCB 11 was previously measured at parts-per-billion (ppb) levels in various printed materials obtained in the US. In this work, PCB 11 was detected in samples of common consumer goods including magazines, advertisements, maps, postcards, brochures, napkins, and garments from 26 countries in five continents at concentrations ranging from 0.27 to 86 ppb. Leaching tests confirmed that PCB 11 could be released from these materials into water. We also examined whether the known sources of PCB 11 were large enough to account for the levels of PCB 11 measured in the air, water, soil and sediment of the Delaware River Basin. A mass flow analysis suggests that the outflows and sequestration of PCB 11 in the basin total between 30 and 280 kg y-1. If PCB 11 concentrations in pigments were at the maximum average (125 ppm) allowed under the Toxic Substances Control Act (TSCA), the estimated input of PCB 11 to the Delaware River Basin would be on the order of 42 kg y-1. Despite the large uncertainty in these numbers, the results suggest that pigments may plausibly account for the levels of PCB 11 measured in the environment.
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