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Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure.


ABSTRACT: Polychlorinated biphenyls (PCBs) are organochlorine pollutants with a worldwide dissemination. We examined telomere length (TL) in peripheral blood cells of 207 individuals with a high body burden of PCBs due to occupational exposure in a transformer recycling company. Whereas TL in granulocytes was not affected, the age-adjusted TL in lymphocytes (?TLLymph) of exposed individuals was significantly shorter than expected [-0.77 kb; 95 % confidence interval (CI) -0.9316; -0.6052; p = 0.0001]. PCB exposure did not affect lymphocyte numbers or T cell receptor excision circle (TREC) levels in T cells, suggesting that PCBs cause loss of telomeric DNA in T cells due to their metabolic activation and antigen-stimulated proliferation. In support of this hypothesis, blood plasma levels of PCB-exposed individuals inhibited expression of telomerase, the telomere elongating enzyme in vitro in antigen-specific T cell proliferation assays. 3-OH-CB28, a downstream metabolite of the lower chlorinated PCB-28 in PCB-exposed individuals (mean blood plasma concentration: 0.185 ± 0.68 ng/mL), inhibited telomerase gene expression within 48 h of incubation in lymphoproliferative assays starting at a concentration of 0.27-6.75 µg/mL and accelerated telomere shortening in long-term cell culture experiments. Accelerated telomere shortening due to PCB exposure may lead to limitations of cell renewal and clonal expansion of lymphocyte populations. As PCB-related immune dysfunctions have been linked to increased susceptibility to infectious diseases and increased risk of cancer, our data provide a possible explanation, for how PCBs could promote infections and cancer through limiting immune surveillance.

SUBMITTER: Ziegler S 

PROVIDER: S-EPMC5225163 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure.

Ziegler Susanne S   Schettgen Thomas T   Beier Fabian F   Wilop Stefan S   Quinete Natalia N   Esser Andre A   Masouleh Behzad Kharabi BK   Ferreira Monica S V MS   Vankann Lucia L   Uciechowski Peter P   Rink Lothar L   Kraus Thomas T   Brümmendorf Tim H TH   Ziegler Patrick P  

Archives of toxicology 20160505 1


Polychlorinated biphenyls (PCBs) are organochlorine pollutants with a worldwide dissemination. We examined telomere length (TL) in peripheral blood cells of 207 individuals with a high body burden of PCBs due to occupational exposure in a transformer recycling company. Whereas TL in granulocytes was not affected, the age-adjusted TL in lymphocytes (∆TL<sub>Lymph</sub>) of exposed individuals was significantly shorter than expected [-0.77 kb; 95 % confidence interval (CI) -0.9316; -0.6052; p = 0.  ...[more]

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