Molecular biology of nickel carcinogenesis

Abstract

The molecular mechanisms of nickel carcinogenesis are discussed and reviewed with emphasis on work done in my laboratory. The most important determinant of nickel carcinogenesis is the ability of the nickel ion to reach relevant targets for carcinogenesis, which involves chromatin and depends on the ability of the nickel compound to enter cells. The mechanisms that regulate the phagocytosis and intracellular dissolution of the highly carcinogenic particulate nickel compounds are discussed, as is the ability of these nickel compounds to enhance the DNA methylation pattern and turn off the expression of critical tumor suppressor genes. These findings show these nickel compounds to be a somewhat unique class of carcinogens.