title: 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 NiCl2are difficult to detect in vitro; hence, a heavy reliance on animal studies exists. NiCl2has previously been classified as a non-genotoxic carcinogen (NGTC); however, after studying the effect of NiCl2on many mechanistic end-points, it has become clear that NiCl2behaves more like a genotoxic carcinogen. The induction of reactive oxygen species (ROS) after treatment with NiCl2along with positive micronuclei results from a preliminary 5-day chronic dose micronucleus study further supports that NiCl2has been misclassified as a NGTC. It is possible that NiCl2causes 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.
authors.affiliation: In Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, Wales, UK.
authors.forename: Leanne
authors.initials: L
authors.lastname: Stannard
authors.affiliation: In Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, Wales, UK.
authors.forename: Shareen H
authors.initials: SH
authors.lastname: Doak
authors.affiliation: Genetic Toxicology, Drug Safety and Metabolism, AstraZeneca R&D, Cambridge, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Doherty
authors.affiliation: In Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, Wales, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Jenkins
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D002274:Carcinogens, Environmental / Q000633:toxicity*; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000209:etiology*; D009532:Nickel / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D002274:Carcinogens, Environmental; D009153:Mutagens; D017382:Reactive Oxygen Species; C022838:nickel chloride; D009532:Nickel; D004247:DNA