title: Search for molecular mechanisms in the genotoxicity of nickel.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, University of Connecticut Medical School, Farmington 06030.
authors.forename: F W
authors.initials: FW
authors.lastname: Sunderman
mesh_terms: 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
chemical_list: D009532:Nickel