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 PCB52 from day 18 and PCB28 and CAM from days 30 on. All PCBs decreased cell proliferation from day 18; only PCB52 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.

Serum polychlorinated biphenyls and leukocyte telomere length in a highly-exposed population: The Anniston Community Health Survey

“…Our results are inconsistent with the findings of prior in vitro studies that observed telomere shortening because of exposure to PCB 153, PCB 126, PCB 52, PCB 28, or 2-(4′-chlorophenyl)-1, 4-benzoquinone (PCB3pQ) (Jacobus et al, 2008; Senthilkumar et al, 2011; Senthilkumar et al, 2012; Xin et al, 2016; Ziegler et al, 2016). Alternative mechanisms by which PCBs may induce telomere lengthening have been proposed (Scinicariello and Buser, 2015).…”

“…In vitro , immortalized human skin keratinocytes, hamster lung fibroblasts, immortalized lymphocytes, or human promyelocytic leukemia cells exposed to PCB 153, PCB 126, PCB 52, PCB 28, or 2-(4′-chlorophenyl)-1, 4-benzoquinone (PCB3pQ), have shortened telomeres (Jacobus et al, 2008; Senthilkumar et al, 2011; Senthilkumar et al, 2012; Xin et al, 2016; Ziegler et al, 2016). Conversely, PCB 138 and PCB 153 upregulate c- myc in vitro (Ghosh et al, 2007; Gribaldo et al, 1998).…”

Hepatocellular carcinoma and the risk of occupational exposure

“…ROS are also able to reduce telomerase activity which can determine telomere shortening. The contribution of all or part of these alterations may facilitate the onset of tumors and more specifically HCC [200][201][202][203][204][205] . At present we have no conclusive data on the relationship between PCBs and HCC and further studies will be needed to establish the causal link.…”

Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation

“…Subsequent publications on air pollution and skin aging from 2011 through 2014 demonstrated that: (a) airborne polychlorinated biphenyls (PBCs) reduced telomerase activity and shorten telomere length in human skin (HaCat) keratinocytes [44]; (b) free radicals and organic nanoparticles reduced human keratinocyte viability by apoptosis [43,45,46]; (c) eczema increased with exposure to PM of 10 microns or less in office indoor environments [47] and; (d) atopic dermatitis and other skin sensitivities or aging endpoints increased with air pollutants that are known to induce increased levels of ROS [48][49][50].…”