Perspectives on the mechanism of nickel carcinogenesis gained from models of in vitro carcinogenesis.

This article briefly reviews the approach taken to understand the mechanism of nickel-induced neoplastic transformation. The initial phases of the studies were focused on particulate nickel compounds and on the regulation of phagocytosis of nickel compounds by cells undergoing transformation. The particulate nickel compounds most potent in inducing cell transformation were selectively phagocytized by cells, whereas those that were not active were not phagocytized. The intracellular fate of phagocytized nickel sulfide particles is discussed as well as the interaction of nickel with chromatin. Phagocytized nickel sulfide particles were dissolved in the cytoplasm of cells by the acidification of vacuoles containing phagocytized particles. Nickel ions released from the phagocytized particles produced selective damage in heterochromatin. The selective effects of nickel on heterochromatin are also discussed and related to its mechanism of carcinogenesis.