Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, PR China.
Department of Occupational Health and Occupational Diseases, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, PR China.
Ecotoxicol Environ Saf. 2021 Jan 15;208:111453. doi: 10.1016/j.ecoenv.2020.111453. Epub 2020 Oct 14.
Trichloroethylene (TCE), an important volatile organic solvent, causes a series of toxic damage to human. Conventional genetic mechanisms cannot fully explain its toxicity and carcinogenicity, indicative of the possible involvement of epigenetic mechanisms. Our study was intended to investigate the epigenetic toxicity and underlying mechanisms of TCE. Data showed that 0.3 mM TCE treatment for 24 h increased the growth of L-02 cells transiently. In contrast, subacute exposure to TCE inhibited cell growth and induced the genomic DNA hypomethylation and histone hyperacetylation. Further studies have revealed the TCE-induced DNA hypomethylation in the promoter regions of tumor-related genes, N-Ras, c-Jun, c-Myc, c-Fos and IGF-II, promoting their protein levels in a time-dependent manner. These results reveal there is a negative relationship existing between DNA hypomethylation and protein expression in tumor-related gene after TCE exposure under specific epigenetic microenvironment, serving as early biomarkers for TCE-associated diseases.
三氯乙烯（TCE）是一种重要的挥发性有机溶剂，对人体造成一系列毒性损伤。传统的遗传机制不能完全解释其毒性和致癌性，表明可能涉及表观遗传机制。我们的研究旨在探讨 TCE 的表观遗传毒性及其潜在机制。研究数据表明，浓度为 0.3mM 的 TCE 处理 24 小时可短暂增加 L-02 细胞的生长。相反，亚急性 TCE 暴露抑制细胞生长，并诱导基因组 DNA 低甲基化和组蛋白高乙酰化。进一步的研究揭示了 TCE 诱导的肿瘤相关基因 N-Ras、c-Jun、c-Myc、c-Fos 和 IGF-II 启动子区域的 DNA 低甲基化，以时间依赖性方式促进其蛋白水平。这些结果表明，在特定的表观遗传微环境下，TCE 暴露后肿瘤相关基因的 DNA 低甲基化与蛋白表达之间存在负相关关系，可作为 TCE 相关疾病的早期生物标志物。
