Toxicogenomic effect of nickel and beyond.

Nickel is widely applied in industrial settings and Ni(II) compounds have been classified as group one human carcinogens. The molecular basis of Ni(II) carcinogenicity has proved complex, for many stress response pathways are activated and yield unexpected Ni(II)-specific toxicology profile. Ni(II)-induced toxicogenomic change has been associated with altered activity of HIF, p53, c-MYC, NFκB and iron and 2-oxoglutarate-dependent dioxygenases. Advancing high-throughput technology has indicated the toxicogenome of Ni(II) involves crosstalk between HIF, p53, c-MYC, NFκB and dioxygenases. This paper is intended to review the network of Ni(II)-induced common transcription-factor-governed pathways by discussing transcriptome alteration, its governing transcription factors and the underlying mechanism. Finally, we propose a putative target network of Ni(II) as a human carcinogen.