Water Insoluble nickel compounds vary in their carcinogenic potency due to a selectivity in the ability of the particles to be phagocytized by target cells. In the acidified phagosomes, ionic nickel is released, ultimately making its way into the nucleus. Ni ions cause an increase in DNA methylation we believe by inhibiting Fe dependent histone demethylases such as those responsible for demethylating H3K9 mono and dimethyl. This results in gene silencing and cell transformation. We are currently trying to prove that inhibition of a histone demethylase JHDM2A by Ni ions is responsible for cell transformation by reversing gene silencing and cell transformation by overexpressing the demethylase or by inducing cell transformation with RNAi against this demethylase. .