miR-34a has been identified as a tumor suppressor microRNA (miRNA) involved in the P53 network. Its expression levels correlate to carcinogenesis, which are generally lower in tumor tissue and higher in response to DNA damage. In this study, the response of miR-34a from exposure to genotoxic agents in human lymphoblastoid TK6 cells was evaluated to assess whether the expression of this miRNA could be used as an early indicator for genotoxic damage in mammalian cells. TK6 cells were treated with seven genotoxic agents with different mode-of-actions (cisplatin, N-ethyl-N-nitrosourea, etoposide, mitomycin C, methyl methanesulphonate, taxol, and X-ray radiation) and a non-genetic toxin (usnic acid) at different concentrations for four hours (except for X-rays) and the expression levels of miR-34a were measured 24 h after the beginning of the treatments. The expression levels of miR-34a were significantly increased by these genetic toxins in a dose-dependent manner, while no significant change in miRNA expression was found in the usnic acid-treated cells. These results suggest that miR-34a can respond to genotoxic insults sensitively; thus, miR-34a expression has the potential to be used to evaluate genotoxicity of agents.

miR-34a 已被鉴定为参与P 53 网络的肿瘤抑制微 RNA (miRNA) 。其表达水平与致癌作用相关，致癌作用通常在肿瘤组织中较低，而对 DNA 损伤的反应则较高。在这项研究中，评估了 miR-34a 对人类淋巴母细胞 TK6 细胞中基因毒性药物的反应，以评估该 miRNA 的表达是否可用作哺乳动物细胞基因毒性损伤的早期指标。TK6 细胞用七种具有不同作用模式的基因毒剂（顺铂、N-乙基-N-亚硝基脲、依托泊苷、丝裂霉素 C、甲基磺酸甲酯、紫杉醇和 X 射线辐射）和非遗传毒素（松萝酸）在不同浓度下 4 小时（X 射线除外）和 miR-34a 的表达水平在治疗开始后 24 小时测量。这些遗传毒素以剂量依赖性方式显着增加了 miR-34a 的表达水平，而在松萝酸处理的细胞中未发现 miRNA 表达发生显着变化。这些结果表明 miR-34a 可以灵敏地响应基因毒性损伤；因此，miR-34a 表达有可能用于评估药物的遗传毒性。