Nickel-Induced Histone Hypoacetylation: The Role of Reactive Oxygen Species

The carcinogenicity of specific insoluble nickel compounds is mainly due to their intracellular generation of Ni2 ion and its suppression on gene transcription, while the inhibition of Ni2 on histone acetylation plays an important role in the suppres-sion or silencing of genes. Recent studies on Ni2 and histone H4 acetylation suggest that Ni2 inhibits the acetylation of histone H4 through binding with its N-terminal histidine-18. It is well known that bound Ni2 readily produces reactive oxygen species (ROS) in vivo, a critical factor inversely related with the occurrence of resistance of mammalian cells to Ni2. Thus, we tried to find the possible role of ROS in the induction of Ni2 on histone acetylation in the present study. We found that a high concentration of Ni2 (no less than 600 M) caused a significant decrease of histone acetylation in human hepatoma cells. This inhibition was shown to result mainly from the influence of Ni