Effects of polychlorinated biphenyls (PCBs) on telomere maintenance in hematopoietic stem cells and progenitor cells

PCBs are persistent organic pollutants that are carcinogenic, 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 be differentiated into granulocytes and monocytes. We exposed HL-60 cells to the PCB126 (dioxin-like) and PCB153 (non-dioxin-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 down regulated. The telomere shelterins TRF1, TRF2, and POT1 were upregulated in granulocytes, TRF2 was upand POT1 down regulated 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 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 exposure. With each 2 With permission of Springer, this chapter was reproduced from accepted manuscript: Xin X, Senthilkumar PK, Schnoor JL, Ludewig G. 2015. Effects of PCB126 and PCB153 on telomerase activity and telomere length in undifferentiated and differentiated HL-60 cells. Environmental science and pollution research international. DOI: 10.1007/s11356-015-5187-y. Copyright: © Springer-Verlag Berlin Heidelberg 2015. My role in this work was to conduct all the experiments, analyze data and prepare the manuscript.