Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry (ATSDR), Centers for Disease Control and Prevention (CDC), 4770 Buford Highway, Mailstop S106-5, Chamblee, GA, 30341, USA.
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Environ Res. 2024 Jun 1;250:118515. doi: 10.1016/j.envres.2024.118515. Epub 2024 Feb 17.
Telomeres are inert DNA sequences (TTAGGG) at the end of chromosomes that protect genetic information and maintain DNA integrity. Emerging evidence has demonstrated that telomere alteration can be closely related to occupational exposure and the development of various disease conditions, including cancer. However, the functions and underlying molecular mechanisms of telomere alteration and shelterin dysregulation after welding fume exposures have not been broadly defined. In this study, we analyzed telomere length and shelterin complex proteins in peripheral blood mononuclear cells (PBMCs) and in lung tissue recovered from male Sprague-Dawley rats following exposure by intratracheal instillation (ITI) to 2 mg/rat of manual metal arc-stainless steel (MMA-SS) welding fume particulate or saline (vehicle control). PBMCs and lung tissue were harvested at 30 d after instillation. Our study identified telomere elongation and shelterin dysregulation in PBMCs and lung tissue after welding fume exposure. Mechanistically, telomere elongation was independent of telomerase reverse transcriptase (TERT) activation. Collectively, our findings demonstrated that welding fume-induced telomere elongation was (a) TERT-independent and (b) associated with shelterin complex dysregulation. It is possible that an alteration of telomere length and its regulatory proteins may be utilized as predictive biomarkers for various disease conditions after welding fume exposure. This needs further investigation.
端粒是染色体末端的惰性 DNA 序列（TTAGGG），可保护遗传信息并维持 DNA 完整性。新出现的证据表明，端粒改变可能与职业暴露和各种疾病状况的发展密切相关，包括癌症。然而，端粒改变和庇护体失调在焊接烟尘暴露后的功能和潜在分子机制尚未得到广泛定义。在这项研究中，我们分析了经气管内滴注（ITI）暴露于 2mg/大鼠手动金属电弧不锈钢（MMA-SS）焊接烟尘颗粒或生理盐水（载体对照）后的雄性 Sprague-Dawley 大鼠外周血单个核细胞（PBMC）和肺组织中的端粒长度和庇护体复合物蛋白。滴注后 30d 采集 PBMC 和肺组织。我们的研究在焊接烟尘暴露后发现了 PBMC 和肺组织中的端粒延长和庇护体失调。从机制上讲，端粒延长与端粒酶逆转录酶（TERT）的激活无关。总的来说，我们的研究结果表明，焊接烟尘诱导的端粒延长是（a）TERT 非依赖性的，（b）与庇护体复合物失调有关。端粒长度及其调节蛋白的改变可能可用作焊接烟尘暴露后各种疾病状况的预测生物标志物。这需要进一步研究。
