端粒长度与端粒酶:环境致癌物接触的早期生物标志物  

Telomere length and telomerase: early biomarkers for environmental carcinogen exposure

作　　者：刘宇[1] 胡贵平 贾光[1] LIU Yu;HU Gui-ping;JIA Guang(School of Public Health,Peking University,Beijing 100191,China;不详)

机构地区：[1]北京大学公共卫生学院,北京100191 [2]北京航空航天大学医学科学与工程学院,北京100191

出　　处：《中国职业医学》2021年第4期457-461,467,共6页China Occupational Medicine

基　　金：国家自然科学基金(91743114,81872598);中国疾病预防控制中心化学污染与健康安全重点实验室开放基金(2020CDCKL02)。

摘　　要：端粒是位于真核细胞线状染色体末端的一段DNA蛋白质复合体,具有稳定染色体的功能。端粒长度的变化与环境致癌物的接触密切相关;端粒修复延长依靠端粒酶的催化和介导。典型环境致癌物多环芳烃(PAHs)接触可通过调控端粒相关基因的表达,从而影响端粒长度的变化;长期接触PAHs可导致周围血白细胞端粒缩短,且呈一定程度的剂量-效应关系。端粒功能异常是砷中毒的重要机制之一,端粒长度的变化可作为砷的接触性生物标志物;但砷接触对端粒长度影响的研究结果尚存在较大差异,因此砷接触对端粒长度影响的一致性及可能的机制尚需进一步研究。大气细颗粒物接触可通过诱发机体的氧化应激和炎症反应,攻击遗传物质,进而影响体内细胞的端粒长度;急性颗粒物接触可在短期内(数小时至数天)增加端粒长度,其后端粒的缩短可能与炎症机制有关。端粒长度和端粒酶活性可作为生物标志物,在环境致癌物所致肿瘤的早期监测、诊断和预后评估中发挥重要作用。Telomere is a DNA-protein complex located at the end of linear chromosome of eukaryotic cells, which has the function of stabilizing chromosome. The change of telomere length is closely related to the exposure to environmental carcinogens. The repair and elongation of telomere rely on the catalysis and mediation of telomerase. Exposure to typical environmental carcinogens polycyclic aromatic hydrocarbons(PAHs) can affect the change of telomere length by regulating the expression of telomere-related genes. Long-term exposure to PAHs can shorten the telomeres of peripheral blood leukocytes in a dose-response relationship. Telomere dysfunction is one of the important mechanisms of arsenic poisoning. The change of telomere length can be used as a biomarker of arsenic exposure. However, there are differences in the research results on the effect of arsenic exposure on telomere length, so the consistency of the effect of arsenic exposure on telomere length and the possible mechanism need to be further studied. Exposure to atmospheric fine particulate matter can attack genetic material by inducing oxidative stress and inflammatory response in the body, and then affect the telomere length of cells in vivo. Acute particulate matter exposure can increase telomere length in a short time(a few hours to a few days), and subsequent telomere shortening may be related to the inflammatory mechanism. Telomere length and telomerase activity can be used as biomarkers and play an important role in monitoring early carcinogenesis, diagnosis and prognosis assessment of cancers caused by environmental carcinogens.

关 键 词：端粒 端粒长度 端粒酶 环境致癌物 生物标志物 多环芳烃 砷 颗粒物 

分 类 号：R135[医药卫生—劳动卫生]