title: 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.
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ziegler
authors.affiliation: Institute for Occupational and Social Medicine, University Hospital of the RWTH Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schettgen
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Beier
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilop
authors.affiliation: Institute for Occupational and Social Medicine, University Hospital of the RWTH Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Quinete
authors.affiliation: Institute for Occupational and Social Medicine, University Hospital of the RWTH Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Esser
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Behzad Kharabi
authors.initials: BK
authors.lastname: Masouleh
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Monica S V
authors.initials: MS
authors.lastname: Ferreira
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Vankann
authors.affiliation: Institute of Immunology, RWTH Aachen University, Aachen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Uciechowski
authors.affiliation: Institute of Immunology, RWTH Aachen University, Aachen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
authors.affiliation: Institute for Occupational and Social Medicine, University Hospital of the RWTH Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraus
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany. pziegler@ukaachen.de.|Institute for Occupational and Social Medicine, University Hospital of the RWTH Aachen, RWTH Aachen University, Aachen, Germany. pziegler@ukaachen.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ziegler
mesh_terms: D001711:Biotransformation; D002274:Carcinogens, Environmental / Q000032:analysis / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015331:Cohort Studies; D004350:Drug Residues / Q000032:analysis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005858:Germany; D006801:Humans; D007157:Immunologic Surveillance / Q000187:drug effects; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D011159:Population Surveillance; D059027:Recycling; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D059506:Telomere Shortening / Q000187:drug effects*; D066007:Toxicokinetics
chemical_list: D002274:Carcinogens, Environmental; C081766:2,4,4'-trichlorobiphenyl; D011078:Polychlorinated Biphenyls; D019098:Telomerase
keywords: Lymphocytes; Occupational exposure; Polychlorinated biphenyls; Telomere