Wetenschappelijke onderzoeken PCB's

Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure. >>

Yueming Zhu, Amanda L Kalen, Ling Li, Hans-J Lehmler, Larry W Robertson,Prabhat C Goswami, Douglas R Spitz, Nukhet Aykin-Burns

ABSTRACT PCBs and PCB metabolites have been suggested to cause cytotoxicity by inducing oxidative stress, but the effectiveness of antioxidant intervention after exposure has not been established. Exponentially growing MCF-10A human breast and RWPE-1 human prostate epithelial cells continuously exposed for 5 days to 3 microM PCBs [Aroclor 1254 (Aroclor), PCB153, and the 2-(4-chlorophenyl)-1,4-benzoquinone metabolite of PCB3 (4ClBQ)] were found to exhibit growth inhibition and clonogenic cell killing, with 4ClBQ having the most pronounced effects. These PCBs were also found to increase steady-state levels of intracellular O(2)(*-) and H(2)O(2) (as determined by dihydroethidium, MitoSOX red, and 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate oxidation). These PCBs also caused 1.5- to 5.0-fold increases in MnSOD activity in MCF-10A cells and 2.5- to 5-fold increases in CuZnSOD activity in RWPE-1 cells. Measurement of MitoSOX red oxidation with confocal microscopy coupled with colocalization of MitoTracker green in MCF-10A and RWPE-1 cells supported the hypothesis that PCBs caused increased steady-state levels of O(2)(*-) in mitochondria. Finally, treatment with either N-acetylcysteine (NAC) or the combination of polyethylene glycol (PEG)-conjugated CuZnSOD and PEG-catalase added 1 h after PCBs significantly protected these cells from PCB toxicity. These results support the hypothesis that exposure of exponentially growing human breast and prostate epithelial cells to PCBs causes increased steady-state levels of intracellular O(2)(*-) and H(2)O(2), induction of MnSOD or CuZnSOD activity, and clonogenic cell killing that could be inhibited by a clinically relevant thiol antioxidant, NAC, as well as by catalase and superoxide dismutase after PCB exposure.

Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in nonmalignant human breast epithelial cells. >>

Venkatasubbaiah A Venkatesha, Sujatha Venkataraman, Ehab H Sarsour, Amanda L Kalen, Garry R Buettner, Larry W Robertson, Hans-Joachim Lehmler, Prabhat C Goswami


ABSTRACT Polychlorinated biphenyls (PCBs) are environmental chemical contaminants believed to adversely affect cellular processes. We investigated the hypothesis that PCB-induced changes in the levels of cellular reactive oxygen species (ROS) induce DNA damage resulting in cytotoxicity. Exponentially growing cultures of human nonmalignant breast epithelial cells (MCF10A) were incubated with PCBs for 3 days and assayed for cell number, ROS levels, DNA damage, and cytotoxicity. Exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) or 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), a metabolite of 4-chlorobiphenyl (PCB3), significantly decreased cell number and MTS reduction and increased the percentage of cells with sub-G1 DNA content. Results from electron paramagnetic resonance (EPR) spectroscopy showed a 4-fold increase in the steady-state levels of ROS, which was suppressed in cells pretreated with catalase. EPR measurements in cells treated with 4-Cl-BQ detected the presence of a semiquinone radical, suggesting that the increased levels of ROS could be due to the redox cycling of 4-Cl-BQ. A dose-dependent increase in micronuclei frequency was observed in PCB-treated cells, consistent with an increase in histone 2AX phosphorylation. Treatment of cells with catalase blunted the PCB-induced increase in micronuclei frequency and H2AX phosphorylation that was consistent with an increase in cell survival. Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing.

Safety measures for prevention of PCB accidents.>>

J Pajari

ABSTRACT This paper attempts to clarify the most common measures available for the fire and electrical engineer in the prevention of polychlorinated biphenyl (PCB) hazards. It points out the risks and the potential for making large risks involved in the use of transformers and capacitors more manageable. The focus in solving the PCB problem is on priority. This should be reflected in the agenda of the workshop: it should discuss not only transformers and capacitors as such, but deal more with questions concerning waste disposal, getting correct information to people on substances containing PCBs and on the proper and nonpanicky handling of such substances. The PCB issue does not lend itself to any black and white solution. Instead, a number of different aspects have to be taken into account. Any solutions arrived at are therefore always compromises between risk evaluation and cost effectiveness. Reduction of PCB risks does not have to result, for example, in an increase in fire risks. It is preferable to move step by step and avoid making irretractable decisions. Alternatives available for replacing PCB-filled devices or the widely used method of refilling PCB-filled transformers with silicone oils are not discussed. Refilling is not dealt with because its capacity to reduce the fire risk sufficiently in locations where these transformers are usually found in northern Europe is not known with certainty.

Plasma polychlorinated biphenyl levels in Dutch preschool children either breast-fed or formula-fed during infancy. >>

S Patandin, N Weisglas-Kuperus, M A de Ridder, C Koopman-Esseboom, W A van Staveren, C G van der Paauw, P J Sauer

ABSTRACT This study examined the influence of lactational and in utero exposure to polychlorinated biphenyls (PCBs) on plasma PCB levels in children.

Plasma PCB levels were measured in 173 children at 3.5 years, of whom 91 were breast-fed and 82 were formula-fed in infancy.

Median plasma PCB levels were 3.6 times higher in breast-fed children (0.75 microgram/L) than in their formula-fed peers (0.21 microgram/L). Breast-feeding period and breast-milk PCB levels were important predictors for PCB levels in the breast-fed group. For children in the formula-fed group, PCB levels were significantly related to their material plasma PCB levels.

PCB levels in Dutch preschool children are related to transfer of maternal PCBs; therefore, strategies should be aimed at reducing maternal PCB body burden.

Long-term neurobehavioral effects of perinatal polychlorinated biphenyl (PCB) exposure in monkeys >>

In recent years, there has been growing concern about the potential long-term neurobe-havioral effects of perinatal polychlorinated biphenyl (PCB) exposure. We have addressed this issue in a series of studies at the Harlow Primate Laboratory. Offspring of rhesus monkeys (Macaca mulatto) exposed to commercial PCB mixtures (Aroclor 1016 or Aroclor 1248) were tested on two-choice discrimination-reversal learning at 1.5 years of age and on delayed spatial alternation, a spatial learning and memory task, at four to six years of age. Deficits in performance were observed on both tasks. The deficit observed on delayed spatial alternation in Aroclor 1248-exposed monkeys was quite dramatic. The monkeys were tested for 80 test sessions, but were never able to achieve control levels of performance. This effect was observed when the monkeys were four to six years of age (young adulthood), even though they had not been exposed to PCBs since they were weaned at four months of age. The pattern of effects on both discrimination-reversal learning and delayed spatial alternation was suggestive of damage to the prefrontal cortex.

A Long term follow-up study; Metabolic and other effects of dioxins, PCBs and PBDEs in adolescent >>

De effecten van perinatale blootstelling aan PCB’s op de immuunrespons. >>

Breast Adipose Tissue Concentrations of Polychlorinated Biphenyls and Other Organochlorines and Breast Cancer Risk >>