Global DNA hypomethylation, rather than reactive oxygen species (ROS), a potential facilitator of cadmium-stimulated K562 cell proliferation

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. (c) 2008 Published by Elsevier Ireland Ltd.