Nickel is well known for carcinogenecity to the human with a great threat a long time. Recently, the harmful heavy metals including cadmium and nickel have been reported to cause cancer by inhibiting DNA repair. In this study, we suggested the novel mechanism of molecular and cellular toxicity of nickel in terms of the transcriptional activation of DNA repair genes, Gadd45a and APE. Our data showed that after treating with low dose of Nickel (20μM) the level of expression from Gadd45 and APE did not show any significant difference, while treating with high dose (200μM) showed decreased level of mRNA expression from Gadd45 and APE. High concentration of nickel imposed apoptosis compared with non-treated cells. This information reveals that nickel toxicity has the significant impact on the inhibition of transcriptional activation of Gadd45 and APE. Further molecular study of nickel toxicity might provide evidences for the cancer prevention and clinical approach. (Cancer Prev Res 12, 187-191, 2007)

Keywords: Nickel, Carcinogenesis, DNA repair, Gadd45a, APE, Transcriptional activation