title: Airborne polychlorinated biphenyls (PCBs) reduce telomerase activity and shorten telomere length in immortal human skin keratinocytes (HaCat).
abstract: PCBs, a group of 209 individual congeners, are ubiquitous environmental pollutants and classified as probable human carcinogens. One major route of exposure is by inhalation of these industrial compounds, possibly daily from inner city air and/or indoor air in contaminated buildings. Hallmarks of aging and carcinogenesis are changes in telomere length and telomerase activity. We hypothesize that semi-volatile PCBs, like those found in inner city air, are capable of disrupting telomerase activity and altering telomere length. To explore this possibility, we exposed human skin keratinocytes to a synthetic Chicago Airborne Mixture (CAM) of PCBs, or the prominent airborne PCB congeners, PCB28 or PCB52 for up to 48 days and determined telomerase activity, telomere length, cell proliferation, and cell cycle distribution. PCBs 28, 52 and CAM significantly reduced telomerase activity from days 18-48. Telomere length was shortened by PCB 52 from day 18 and PCB 28 and CAM from days 30 on. All PCBs decreased cell proliferation from day 18; only PCB 52 produced a small increase of cells in G0/G1 of the cell cycle. This significant inhibition of telomerase activity and reduction of telomere length by PCB congeners suggest a potential mechanism by which these compounds could lead to accelerated aging and cancer.
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, United States.
authors.forename: P K
authors.initials: PK
authors.lastname: Senthilkumar
authors.forename: A J
authors.initials: AJ
authors.lastname: Klingelhutz
authors.forename: J A
authors.initials: JA
authors.lastname: Jacobus
authors.forename: H
authors.initials: H
authors.lastname: Lehmler
authors.forename: L W
authors.initials: LW
authors.lastname: Robertson
authors.forename: G
authors.initials: G
authors.lastname: Ludewig
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000009:adverse effects* / Q000494:pharmacology; D019098:Telomerase / Q000187:drug effects* / Q000378:metabolism; D016615:Telomere / Q000187:drug effects*
chemical_list: D000393:Air Pollutants; C009407:2,5,2',5'-tetrachlorobiphenyl; C081766:2,4,4'-trichlorobiphenyl; D011078:Polychlorinated Biphenyls; D019098:Telomerase