Search for molecular mechanisms in the genotoxicity of nickel.
This paper reviews recent studies done in the author's laboratory on molecular mechanisms of nickel genotoxicity, using as an experimental model the teratogenic effects of bivalent nickel ions (Ni2+) in South Africa frogs (Xenopus laevis). A Ni(2+)-binding protein, pNiXa, was identified in Xenopus oocytes and embryos (molecular weight 45 kDa, isoelectric point approximately 8.5) with a strong homology to human alpha 1-antitrypsin, alpha 1-antichymotrypsin, and other serine proteinase inhibitors. CNBr peptides of pNiXa showed sequence identity to Ep45. Nondenatured pNiXa, purified by nickel affinity chromatography, inhibits bovine alpha 1-chymotrypsin. The possibility that pNiXa plays a key role in Ni2+ teratogenesis is indicated by (i) the avidity of pNiXa for Ni2+, (ii) the presence of pNiXa when the embryos are susceptible to Ni2+ teragenesis, and (iii) the potential of the (HX)n-motif to form Ni2+ complexes that could catalyze the formation of oxygen free radicals and thereby damage deoxyribonucleic acid (DNA) and chromosomes.
Sunderman
F W
FW
Department of Laboratory Medicine, University of Connecticut Medical School, Farmington 06030.
D000014:Abnormalities, Drug-Induced; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D004625:Embryo, Nonmammalian / Q000187:drug effects; D008969:Molecular Sequence Data; D009532:Nickel / Q000378:metabolism / Q000633:toxicity*; D011485:Protein Binding; D014982:Xenopus laevis
D009532:Nickel