The Biological Chemistry of Nickel
CHAPTER 3: Nickel Toxicity and Carcinogenesis
Published:24 Mar 2017
Jason Brocato, Max Costa, 2017. "Nickel Toxicity and Carcinogenesis", The Biological Chemistry of Nickel, Deborah Zamble, Magdalena Rowińska-Żyrek, Henryk Kozlowski
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Nickel is the 24th most abundant element in the earth's crust and makes up about 3% of the composition of the earth. It is the fifth most abundant element by weight after iron, oxygen, magnesium, and silicon. The metal is a well-established class I human carcinogen. In vitro mutation assays in Salmonella and mammalian cells have shown that nickel compounds have low mutagenic capabilities; therefore, its role in carcinogenesis is thought to be largely through epigenetic mechanisms. Various investigations have demonstrated nickel's ability to perturb the DNA methylome, induce changes in global histone modifications, and alter the expression of microRNAs. The changes to the epigenome observed after nickel exposure mirrors the epigenetic landscape of cancer cells. Global DNA hypomethylation and global histone hypoacetylation, two hallmark traits of cancer cells, occur after nickel exposure. Nickel also has been shown to alter the expression of several microRNAs associated with cancer. Tumor-suppressing microRNAs, those whose target mRNAs are oncogene transcripts, may be turned off after nickel treatment, while oncogenic microRNAs, those whose target mRNAs are tumor-suppressing transcripts, may be enhanced. This chapter will give a brief introduction to toxicology and epigenetics and take a deeper look into the carcinogenicity of nickel by describing several epigenetic mechanisms that mediate its carcinogenic potential.