Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, United States.
Toxicol Lett. 2011 Jul 4;204(1):64-70. doi: 10.1016/j.toxlet.2011.04.012. Epub 2011 Apr 21.
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 PCB 52 from day 18 and PCB 28 and CAM from days 30 on. All PCBs decreased cell proliferation from day 18; only PCB 52 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.
多氯联苯（PCBs）是一组由 209 种单体组成的化合物，是无处不在的环境污染物，被归类为可能的人类致癌物。接触这些工业化合物的主要途径之一是吸入这些化合物，可能每天都会从城市内部空气和/或污染建筑物内的室内空气中吸入。衰老和致癌的标志是端粒长度和端粒酶活性的变化。我们假设，像在城市内部空气中发现的半挥发性 PCBs，能够破坏端粒酶活性并改变端粒长度。为了探索这种可能性，我们将人类皮肤角质细胞暴露于合成的芝加哥空气混合物（CAM）的 PCBs 或突出的空气传播 PCB 同系物 PCB28 或 PCB52 中，长达 48 天，并确定端粒酶活性、端粒长度、细胞增殖和细胞周期分布。PCBs28、52 和 CAM 从第 18 天到第 48 天显著降低了端粒酶活性。从第 18 天开始，PCB52 缩短了端粒长度，而 PCB28 和 CAM 则从第 30 天开始缩短了端粒长度。所有 PCBs 从第 18 天开始降低细胞增殖；只有 PCB52 使细胞周期的 G0/G1 期的细胞略有增加。这些 PCB 同系物对端粒酶活性的显著抑制和端粒长度的减少表明，这些化合物可能导致加速衰老和癌症的潜在机制。
