Carcinogenic effect of nickel compounds

Abstract

Nickel is a widely distributed metal that is industrially applied in many forms. Accumulated epidemiological evidence confirms that exposures to nickel compounds are associated with increased nasal and lung cancer incidence, both in mostly occupational exposures. Although the molecular mechanisms by which nickel compounds cause cancer are still under intense investigation, the carcinogenic actions of nickel compounds are thought to involve oxidative stress, genomic DNA damage, epigenetic effects, and the regulation of gene expression by activation of certain transcription factors related to corresponding signal transduction pathways. The present review summarizes our current knowledge on the molecular mechanisms of nickel carcinogenesis, with special emphasis on the role of nickel induced reactive oxygen species (ROS) and signal transduction pathways.

In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

“…These synergistic epigenetic effects are further corroborated by statistically significant reduction of H3-Ser10 phosphorylation caused by tungsten-alloy as compared to cobalt concentration (CoA) equivalent to the percentage that was used in the preparation of tungsten-alloy in C2C12 cells. When cobalt and tungsten carbide particles are in close contact, the generation of reactive oxygen species may take place, disturbing signaling pathways involved in proliferation, apoptosis, transformation, and senescence (Lison et al, 1995;Lu, et al, 2005). Tungsten carbide-cobalt mixture has been shown to trigger DNA fragmentation and rearrangements of nucleosome/chromatin assembly in human peripheral blood mononucleated cells thus contributing to apoptosis (Lombaert et al, 2004(Lombaert et al, , 2008.…”

The Requirement of c-Jun N-terminal Kinase 2 in Regulation of Hypoxia-inducing Factor-1α mRNA Stability

“…The causality between nickel exposure and cancer development has been supported by both animal studies and epidemiologic investigations (2). It was reported that both the genetic and epigenetic factors were attributable to the carcinogenic characteristics of mode of action for nickel (3,4). Induction of hypoxia-inducible factor-1␣ (HIF-1␣) 3 by nickel treatment was documented both in vivo and in vitro (5).…”

Interactions by Carcinogenic Metal Compounds with DNA Repair Processes

“…Water soluble nickel salts are taken up only slowly by cells, while particulate of nickel compounds are phagocytosed and, due to the low pH, gradually dissolved in lysosomes, yielding high concentrations of nickel ions in the nucleus . Using in vitro cells and animal models, nickel compounds have been found to generate various types of adverse effects, including chromosomal aberrations, DNA strand breaks, high reactive oxygen species production, impaired DNA repair, hypoxia-mimic stress, aberrant epigenetic changes, and signaling cascade activation (Lu et al, 2005). Nickel has been shown to interfere with the repair mechanisms involved in removing UV-, platinum-, mitomycin C, g-radiation-and benzo[a]pyrene-induced DNA damage (Dally et al, 1997;Hartmann et al, 1998;Schwerdtle et al, 2002).…”