Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, United States of America.
Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, WI, United States of America.
Pharmacol Ther. 2021 Apr;220:107742. doi: 10.1016/j.pharmthera.2020.107742. Epub 2020 Nov 8.
The ends of chromosomes shorten at each round of cell division, and this process is thought to be affected by occupational exposures. Occupational hazards may alter telomere length homeostasis resulting in DNA damage, chromosome aberration, mutations, epigenetic alterations and inflammation. Therefore, for the protection of genetic material, nature has provided a unique nucleoprotein structure known as a telomere. Telomeres provide protection by averting an inappropriate activation of the DNA damage response (DDR) at chromosomal ends and preventing recognition of single and double strand DNA (ssDNA and dsDNA) breaks or chromosomal end-to-end fusion. Telomeres and their interacting six shelterin complex proteins in coordination act as inhibitors of DNA damage machinery by blocking DDR activation at chromosomes, thereby preventing the occurrence of genome instability, perturbed cell cycle, cellular senescence and apoptosis. However, inappropriate DNA repair may result in the inadequate distribution of genetic material during cell division, resulting in the eventual development of tumorigenesis and other pathologies. This article reviews the current literature on the association of changes in telomere length and its interacting proteins with different occupational exposures and the potential application of telomere length or changes in the regulatory proteins as potential biomarkers for exposure and health response, including recent findings and future perspectives.
染色体的末端在每一轮细胞分裂中都会缩短，而这一过程被认为受到职业暴露的影响。职业危害可能会改变端粒长度的内稳态，导致 DNA 损伤、染色体异常、突变、表观遗传改变和炎症。因此，为了保护遗传物质，大自然提供了一种独特的核蛋白结构，称为端粒。端粒通过避免在染色体末端不适当激活 DNA 损伤反应 (DDR) 并防止识别单链和双链 DNA (ssDNA 和 dsDNA) 断裂或染色体端到端融合来提供保护。端粒及其相互作用的六个 shelterin 复合物蛋白协调作用，通过阻断 DDR 在染色体上的激活，充当 DNA 损伤机制的抑制剂，从而防止基因组不稳定性、细胞周期紊乱、细胞衰老和细胞凋亡的发生。然而，不适当的 DNA 修复可能导致细胞分裂过程中遗传物质的分配不均，最终导致肿瘤发生和其他病理变化。本文综述了目前关于端粒长度及其相互作用蛋白与不同职业暴露的变化的相关文献，以及端粒长度或调控蛋白变化作为暴露和健康反应的潜在生物标志物的潜在应用，包括最近的发现和未来的展望。
