NDLI: Effects of PCB126 and PCB153 on telomerase activity and telomere length in undifferentiated and differentiated HL-60 cells

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Effects of PCB126 and PCB153 on telomerase activity and telomere length in undifferentiated and differentiated HL-60 cells

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ludewig, Gabriele Xin, Xing Senthilkumar, P. K. Schnoor, Jerald L.
Description	Country affiliation: United States Author Affiliation: Xin X ( Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, USA.); Senthilkumar PK ( Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, USA.); Schnoor JL ( Risk Evaluation Branch, Center for Disease Control and Prevention, Cincinnati, OH, 45226, USA.); Ludewig G ( Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, USA.)
Abstract	PCBs are persistent organic pollutants that are carcinogenic and immunotoxic and have developmental toxicity. This suggests that they may interfere with normal cell maturation. Cancer and stem/progenitor cells have telomerase activity to maintain and protect the chromosome ends, but lose this activity during differentiation. We hypothesized that PCBs interfere with telomerase activity and the telomere complex, thereby disturbing cell differentiation and stem/progenitor cell function. HL-60 cells are cancer cells that can differentiated into granulocytes and monocytes. We exposed HL-60 cells to PCB126 (dioxin-like) and PCB153 (nondioxin-like) 6 days before and during 3 days of differentiation. The differentiated cells showed G0/G1 phase arrest and very low telomerase activity. hTERT and hTR, two telomerase-related genes, were downregulated. The telomere shelterins TRF1, TRF2, and POT1 were upregulated in granulocytes, and TRF2 was upregulated and POT1 downregulated in monocytes. Both PCBs further reduced telomerase activity in differentiated cells, but had only small effects on the differentiation and telomere-related genes. Treatment of undifferentiated HL-60 cells for 30 days with PCB126 produced a downregulation of telomerase activity and a decrease of hTERT, hTR, TRF1, and POT1 gene expression. With PCB153, the effects were less pronounced and some shelterin genes were increased after 30 days of exposure. With each PCB, no differentiation of cells was observed and cells continued to proliferate despite reduced telomerase activity, resulting in shortened telomeres after 30 days of exposure. These results indicate cell-type and PCB congener-specific effects on telomere/telomerase-related genes. Although PCBs do not seem to strongly affect differentiation, they may influence stem or progenitor cells through telomere attrition with potential long-term consequences for health.
ISSN	09441344
Issue Number	3
Volume Number	23
e-ISSN	16147499
Journal	Environmental Science and Pollution Research
Language	English
Publisher	Springer
Publisher Date	2016-02-01
Publisher Place	Germany
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cell Differentiation Drug Effects Enzyme Inhibitors Toxicity Polychlorinated Biphenyls Telomerase Antagonists & Inhibitors Telomere Metabolism Chemistry Gene Expression Hl-60 Cells Humans Genetics Journal Article Research Support, N.i.h., Extramural Discipline Environmental Science Discipline Environmental Chemistry
Content Type	Text
Resource Type	Article
Subject	Environmental Chemistry Health, Toxicology and Mutagenesis Pollution Medicine

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