Mechanisms of nickel carcinogenesis.
Recent investigations on possible mechanisms of nickel carcinogenesis are reviewed, emphasizing cellular uptake and intracellular translocation of nickel, morphological transformation of cells by nickel compounds, chromosomal damage, DNA strandbreaks and DNA-protein complexes produced by nickel compounds, mutagenic effects of nickel, influence of nickel on the helical transition of B-DNA to Z-DNA, nickel-induced infidelity of DNA synthesis, free radicals and lipid peroxidation induced by nickel exposures, nickel inhibition of DNA repair, nickel as a tumor promotor, nickel inhibition of natural-killer (NK) cell activity, manganese and magnesium antagonism of nickel carcinogenesis, and speculation that Ni2+ might replace Zn2+ in finger-loop domains of transforming proteins. The weight of evidence supports the following tentative conclusions: differences in the carcinogenic activities of nickel compounds may reflect variations in their capacities to provide nickel ions (eg, Ni2+) at critical sites within target cells; Ni2+ can initiate carcinogenesis, possibly by mutagenesis, chromosome damage, formation of Z-DNA, inhibition of DNA excision-repair or epigenetic mechanisms; Ni2+ can function as a tumor promoter; Ni2+ can enhance tumor progression by inhibiting NK cell activity; and nickel carcinogenesis can be suppressed or modified by certain other metals (eg, manganese and magnesium).
Sunderman
F W
FW
Department of Laboratory Medicine, University of Connecticut Medical School, Farmington.
D000818:Animals; D002273:Carcinogens; D002869:Chromosome Aberrations; D004247:DNA / Q000187:drug effects; D005609:Free Radicals; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects; D050356:Lipid Metabolism; D008274:Magnesium / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D009153:Mutagens; D009532:Nickel / Q000009:adverse effects* / Q000378:metabolism; D014170:Transformation, Genetic / Q000187:drug effects
D002273:Carcinogens; D005609:Free Radicals; D009153:Mutagens; D008345:Manganese; D009532:Nickel; D004247:DNA; D008274:Magnesium