Triclosan reduces the levels of global DNA methylation in HepG2 cells

Triclosan (TCS), an antibacterial agent, is widely used in a variety of personal care and industrial products. TCS is associated with the development of liver tumors in rodents and has become a concern to environmental and human health. This study is aimed at investigating whether TCS could modulate the levels of global DNA methylation (GDM) in human hepatocytes. We found that treatment with different doses (1.25-10 mu M) of TCS did not affect HepG2 cell viability, but significantly reduced the levels of GDM in HepG2 cells, and inhibited DNMT1 activity. Furthermore, treatment with TCS significantly inhibited the methylated DNA-binding domain 2 (MBD2), MBD3, and MeCP2 mRNA transcription. In addition, treatment with TCS promoted the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) in a dose-dependent manner, which was abrogated by treatment with an antioxidant, N-acetylcysteine (NAC). Collectively, our data indicated that TCS reduced the levels of GDM and down-regulated the MBD2, MBD3, and MeCP2 gene expression by increasing 8-OHdG levels and inhibiting the DNMT1 activity in HepG2 cells. (C) 2012 Elsevier Ltd. All rights reserved.