A Review of Genetic and Epigenetic Mechanisms in Heavy Metal Carcinogenesis: Nickel and Cadmium

Abstract. Heavy metals constitute an important class of environmental contaminants that classified as human carcinogens according to the US Environmental Protection Agency and the International Agency for Research on Cancer. They affect human health through occupational and environmental exposure. Multiple experimental epidemiological studies indicate that heavy metals such as Nickel and Cadmium can induce several types of cancer significantly pulmonary cancers, but the mechanisms underlying the carcinogenesis are not well understood yet. This metals are genotoxic elements for human, while they are typically weak mutagens, indicating that indirect mechanisms may be primary responsible for their genotoxicity. Several studies suggest that epigenetic mechanisms may play an important role in metal-induced carcinogenesis. Here, we review studies that investigate the common mechanisms of nickel and cadmium-induced carcinogenesis, include DNA methylation, histone modification, induction of oxidative stress, interference with DNA repair system, and interruption of cell growth and proliferation through signaling pathway and dysregulation of tumor suppressor genes.