Huang Dejun, Zhang Yingmei, Qi Yongmei, Chen Che, Ji Weihong
Key Laboratory of Arid and Grassland Ecology, School of Life Sciences, Lanzhou University, Lanzhou, PR China.
Toxicol Lett. 2008 Jun 10;179(1):43-7. doi: 10.1016/j.toxlet.2008.03.018. Epub 2008 Apr 8.
Cell proliferation plays a critical role in the process of cadmium (Cd) carcinogenesis. Although both induction of reactive oxygen species (ROS) and alteration of DNA methylation are involved in Cd-stimulated cell proliferation, the detailed mechanism of Cd-stimulated cell proliferation remains poorly understood. In this study, K562 cells pre-treated with N-acetylcysteine (NAC) or methionine (Meth) were exposed to Cd to investigate the potential contribution of ROS and global DNA methylation pathways in Cd-induced cell proliferation. The results showed that Cd-stimulated cell proliferation, increased ROS and DNA damage levels, and induced global DNA hypomethylation. The increases of ROS and DNA damage levels were attenuated by pre-treatment with NAC. Cd-stimulated cell proliferation did not appear to be suppressed through eliminating ROS by NAC. However, methionine was shown to prevent Cd-induced global DNA hypomethylation and Cd-stimulated cell proliferation. Our results suggest that global DNA hypomethylation, rather than ROS, is a potential facilitator of Cd-stimulated K562 cell proliferation.
细胞增殖在镉（Cd）致癌过程中起着关键作用。尽管活性氧（ROS）的诱导和DNA甲基化的改变都与镉刺激的细胞增殖有关，但镉刺激细胞增殖的详细机制仍知之甚少。在本研究中，用N-乙酰半胱氨酸（NAC）或蛋氨酸（Meth）预处理的K562细胞暴露于镉，以研究ROS和整体DNA甲基化途径在镉诱导的细胞增殖中的潜在作用。结果表明，镉刺激细胞增殖，增加ROS和DNA损伤水平，并诱导整体DNA低甲基化。NAC预处理可减轻ROS和DNA损伤水平的增加。NAC消除ROS似乎并未抑制镉刺激的细胞增殖。然而，蛋氨酸可防止镉诱导的整体DNA低甲基化和镉刺激的细胞增殖。我们的结果表明，整体DNA低甲基化而非ROS是镉刺激K562细胞增殖的潜在促进因素。
