Polychlorinated Biphenyls are an "Old" Issue:Telomere Toxicity Accelerates Senescence and Promotes Carcinogenesis

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Project Period: 
2006
Project Investigator(s): 
J. Jacobus, Interdisciplinary Degree in Toxicology, G. Ludewig, Department of Occupational and Environmental Health, University of Iowa
A. Klingelhutz, Department of Microbiology, University of Iowa
Abstract: 

Polychlorinated Biphenyls (PCBs) are persistent organic pollutants classified as "probable human carcinogens" by the US Environmental Protection Agency. The exact mechanism of PCB carcinogenesis continues to be elusive. This pilot study proposes techniques for the investigation of a novel target of PCB toxicity, the telomere. Telomeres are rapidly being recognized by scientists as key cellular factors in carcinogenesis, cell-signaling, and senescence. Oxidative stress has been shown to shorten telomeres and therefore reduce the protective buffer they provide to the chromosome. Researchers have implicated oxidative stress as the ultimate carcinogen resultant from PCB exposure. However, no study has examined a telomeric toxicity arising from PCB metabolism. Positive findings in this study could open up an entirely new line of innovative interdisciplinary research, while providing a unifying explanation to the often contradictory findings in PCB carcinogenesis.

Publications: 

Senthilkumar PK, Klingelhutz AJ, Jacobus JA, Lehmler H, Robertson LW, Ludewig G; Airborne Polychlorinated Biphenyls (PCBs) Reduce Telomerase Activity and Shorten Telomere Length in Immortal Human Skin Keratinocytes (HaCat). Toxicol Lett. 2011; 204(1):64-70.