Is Nickel Chloride really a Non-Genotoxic Carcinogen?

Abstract

Human beings are exposed to carcinogens through air, water, food and tobacco smoke. Nickel chloride (NiCl2) is a toxic and carcinogenic environmental and occupational pollutant, which was previously classified as a non-genotoxic carcinogen and thought to not directly alter the DNA. Non-genotoxic carcinogens such as NiCl2 are difficult to detect in vitro; hence, a heavy reliance on animal studies exists. NiCl2 has previously been classified as a non-genotoxic carcinogen (NGTC); however, after studying the effect of NiCl2 on many mechanistic end-points, it has become clear that NiCl2 behaves more like a genotoxic carcinogen. The induction of reactive oxygen species (ROS) after treatment with NiCl2 along with positive micronuclei results from a preliminary 5-day chronic dose micronucleus study further supports that NiCl2 has been misclassified as a NGTC. It is possible that NiCl2 causes indirect DNA damage by the production of ROS and requires a longer, chronic exposure, which is more similar to that of human exposure. The focus of this MiniReview is on research into the molecular mechanisms of nickel-induced carcinogenicity and potential genotoxicity, with a focus on one of the salts of greatest commercial importance, nickel chloride.