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Journal of Cancer Prevention


Cancer prevention research 2007; 12(3): 187-191

Published online September 30, 2007

© Korean Society of Cancer Prevention

Study on the Novel Carcinogenic Pathway of Heavy Metal Nickel:Inhibition of Transcriptional Activation of DNA Repair Gene Gadd45a and APE

Seok Won Chung1, Jeong Won Hwang1, Se Jin Oh1, Byung Joo Kim1, Hwa Jin Jung1,Chulwoo Lee2, Jae-Chun Ryu3 and Young Rok Seo1


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

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