Background: Acute exposure to nickel alters the pattern of gene expression in normal cells and induces a pattern of gene expression similar to that found in nickel-induced cancers. This study aims to review various mechanisms in nickel carcinogenesis.

Materials and Methods: A systematic search on the Pubmed and Google scholar databases was done on the carcinogenic potency of nickel compounds in animal models and rodent cells in vitro.

Results: Published evidence confirmed that the epigenetic activity of nickel carcinogenic compounds may be exerted with a modulation of gene expression. Nickel plays a role in the derivation of cells with neoplastic properties. Many researches demonstrated that nickel depletes intracellular ascorbate and may be able to replace the iron in the active site of hypoxia inducible factor-1a (HIF-1a) hydroxylases, which results in the inhibition of prolyl hydroxylase activity, activation of of hypoxia inducible factor-1a (HIF-1a), a protein known to be over-expressed in a variety of cancers and expression of hypoxia-inducible genes such as Cap43 gene. Cap43 gene was found to be highly inducible by hypoxia and over-expressed in cancer cells. These studies demonstrate that human exposure to Nickel turns on signaling for hypoxic stress, which may be important in its carcinogenesis.

Conclusion: The major epigenetic effects of nickel are depletion of ascorbate, inhibition of prolyl hydroxylase enzyme activity, the stabilization of hypoxia inducible factor-1a (HIF-1a and expression of hypoxia-inducible genes such as Cap43 gene.