A New Player in Environmentally Induced Oxidative Stress: Polychlorinated Biphenyl Congener, 3,3' dichlorobiphenyl (PCB11).
ABSTRACT 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.Environmental Science and Pollution Research 07/2015; DOI:10.1007/s11356-015-4987-4 · 2.76 Impact Factor
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ABSTRACT: Lower chlorinated PCBs, such as PCB3, are air contaminants in buildings and outdoors. Metabolites of PCB3 are potential endocrine disrupting chemicals and genotoxic agents. We studied the disposition of phenolic and sulfated metabolites after acute nose-only inhalation exposure to airborne PCB3 for 2 h in female rats. Inhalation exposure was carried out in three groups. In the first group, rats exposed to an estimated inhaled dose of 23 µg/rat were euthanized at 0, 1, 2, and 4 h after exposure. Highest concentrations of phenols and sulfates were observed at 0 h, and the values were 7±1 and 560± 60 ng/mL in serum, 213±120 and 842± 80 ng/g in liver, 31±27 and 22±7 ng/g in lung, and 27±6 and 3±0 ng/g in brain, respectively. First order serum clearance half-lives of 0.5 h for phenols and 1 h for sulfates were estimated. In the second group, rats exposed to an estimated inhaled dose of 35 µg/rat were transferred to metabolism cages immediately after exposure for the collection of urine and feces over 24 h. Approximately 45±5% of the dose was recovered from urine and consisted mostly of sulfates, and 18±5% of the dose recovered from feces was exclusively phenols. Unchanged PCB3 was detected in both urine and feces but accounted only for 5±3% of the dose. Peak excretion of metabolites in both urine and feces occurred within 18 h post exposure. In the third group, three bile-cannulated rats exposed to an estimated dose of 277 µg/rat were used for bile collection. Bile was collected for 4 h immediately after 2 h exposure. Biliary metabolites consisted mostly of sulfates, some glucuronide, and lower amounts of the free phenol. Control rats in each group were exposed to clean air. Clinical serum chemistry values, serum T4 level, and urinary 8-hydroxy-2'-deoxyguanosine were similar in treated and control rats. These data show that PCB3 is rapidly metabolized to phenols and conjugated to sulfates after inhalation and both of these metabolites are distributed to liver, lungs and brain. The sulfates elaborated into bile are either reabsorbed or hydrolyzed in the intestine and excreted in the feces as phenols.Chemical Research in Toxicology 07/2014; 27(8). DOI:10.1021/tx500150h · 4.19 Impact Factor
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ABSTRACT: Environmental exposures that affect accumulation of polychlorinated biphenyls (PCBs) in humans are complex and not fully understood. One challenge in linking environmental exposure to accumulation is determining variability of PCB concentrations in samples collected from the same person at different times. We hypothesized that PCBs in human blood serum are consistent from year to year in people who live in the same environment between sampling. We analyzed blood serum from children and their mothers from urban and rural U.S. communities (n=200) for all 209 PCBs (median ΣPCBs=45 ng/g lw) and 12 hydroxylated PCBs (median ΣOH-PCBs=0.09 ng/g fw). A subset of these participants (n=155) also had blood PCB and OH-PCB concentrations analyzed during the previous calendar year. Although many participants had similar levels of PCBs and OH-PCBs in their blood from one year to the next, some participants had surprisingly different levels. Year-to-year variability in ΣPCBs ranged from -87% to 567% and in ΣOH-PCBs ranged from -51 to 358% (5th-95th percentile). This is the first study to report variability of all PCBs and major metabolites in two generations of people and suggests short-term exposures to PCBs may be a significant component of what is measured in human serum.Environmental Science and Technology 10/2014; 48(22). DOI:10.1021/es502490w · 5.48 Impact Factor