PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

Senthilkumar, P.; Robertson, Larry W.; Ludewig, Gabriele

doi:10.1016/j.taap.2011.12.015

Cited by 31 publications

(28 citation statements)

References 68 publications

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“…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).…”

Section: Discussioncontrasting

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Callahan

Pavúk

Birnbaum

et al. 2017

Environment International

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Background Serum polychlorinated biphenyls (PCBs) have previously been associated with longer leukocyte telomere length (LTL) in most, but not all, of the few previous studies. PCBs were produced in Anniston, Alabama from 1929–1971 and participants of the Anniston Community Health Survey (ACHS) were highly exposed. Objectives We evaluated serum levels of 35 PCBs and relative telomere length in 559 ACHS participants. Methods Relative LTL was measured in DNA extracted from blood clots. We assessed PCBs individually, grouped by chlorination, and summed PCBs. We used linear regression to assess the association between each PCB metric while adjusting for pertinent covariates. Results Serum PCBs were associated with longer LTL among white participants and the oldest age group of black participants. Among white participants, compared with those in the first quartile of sum PCBs those in the third quartile of sum PCBs had 8.09% longer relative LTL (95% CI: 1.99; 14.55) and those in the fourth had 7.58% longer relative LTL (95%CI: −0.01; 15.76) (p-quadratic = 0.05). Among African American participants, serum PCBs were associated with longer relative LTL among those over age 64 only. Tests for interaction were not statistically significant. Conclusions We observed a non-linear positive association between serum PCBs and LTL among white participants. Serum PCBs were associated with longer LTL in the oldest age group of African Americans. This association may provide insight into the cancers previously associated with exposure to PCBs, melanoma and non-Hodgkin lymphoma, which have been associated with long LTL in previous studies.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Callahan

Pavúk

Birnbaum

et al. 2017

Environment International

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“…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.…”

Section: Polychlorinated Biphenylsmentioning

confidence: 99%

Hepatocellular carcinoma and the risk of occupational exposure

Rapisarda

Loreto

Malaguarnera

et al. 2016

WJH

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The main risk factors for HCC are alcoholism, hepatitis B virus, hepatitis C virus, nonalcoholic steatohepatitis, obesity, type 2 diabetes, cirrhosis, aflatoxin, hemochromatosis, Wilson's disease and hemophilia. Occupational exposure to chemicals is another risk factor for HCC. Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent. This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem. Core tip: Hepatocellular carcinoma (HCC) is the fifth most common human cancer. This review summarizes current knowledge regarding the occupational risk factors of HCC. In particular, we underline not only the infective but also non-infective occupational risk exposure, including chemical agents and toxic metabolites which are a major cause of liver damage.

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“…Several studies investigating telomere dynamics in PCB-exposed individuals or PCB-treated telomerase positive tumor cell lines have been published (Xin et al 2016; Jacobus et al 2008; Shin et al 2010; Senthilkumar et al 2011, 2012; Mitro et al 2015). Whereas in two population-based studies low dose exposure to non-ortho PCBs was associated with longer TL in leukocytes (Shin et al 2010; Mitro et al 2015), long-term treatment of cell lines with PCBs resulted in cell-type and PCB congener-specific adverse effects on TL, htert activity and expression of telomere-associated shelterin genes (Xin et al 2016; Jacobus et al 2008; Senthilkumar et al 2011, 2012). Based on these recent findings, we selectively analyzed TL of granulocytes and lymphocytes in peripheral blood from individuals occupationally exposed to very high levels of PCBs.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1725-8) contains supplementary material, which is available to authorized users.

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PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

Cited by 31 publications

References 68 publications

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

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

Hepatocellular carcinoma and the risk of occupational exposure

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

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