Nickel(II) interferes with the incision step in nucleotide excision repair in mammalian cells.

Nickel compounds are carcinogenic to humans and experimental animals. However, the mechanisms leading to tumor formation are still not understood since the mutagenic potential is rather weak. In contrast, nickel(II) enhances the cytotoxicity and genotoxicity in combination with several other DNA-damaging agents. To elucidate possible interactions with DNA repair processes, the effect of nickel(II) on the nucleotide excision repair pathway has been investigated after UV irradiation in HeLa cells. Nickel(II) blocks the removal of cyclobutane pyrimidine dimers as determined by T4 endonuclease V-sensitive sites. When the alkaline unwinding technique was applied, significantly less transient DNA strand breaks after UV irradiation were detected in the presence of nickel(II) compared to UV alone, suggesting an inhibition of the incision step of nucleotide excision repair. Once incisions are made, the ligation of repair patches is delayed as well in nickel-treated cells, as observed by the alkaline unwinding and nucleoid sedimentation techniques. This inhibition of DNA repair is partly reversible by the addition of magnesium(II), indicating that the competition between Ni2+ and Mg2+ may provide an important mechanism for the disturbance of DNA-protein interactions involved in the repair process. Since the repair inhibition is observed at noncytotoxic concentrations of nickel(II), it may well be relevant for its carcinogenic action.

[1]  A. Hartwig,et al.  Mechanisms in nickel genotoxicity: the significance of interactions with DNA repair. , 1994, Toxicology Letters.

[2]  L. Loeb,et al.  Nickel induces a signature mutation for oxygen free radical damage. , 1993, Cancer research.

[3]  Y. Sugiura,et al.  Alteration of DNA binding specificity by nickel (II) substitution in three zinc (II) fingers of transcription factor Sp1. , 1993, Biochemical and biophysical research communications.

[4]  P. Chambon,et al.  DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. , 1993, Science.

[5]  J. Hoeijmakers,et al.  Genes controlling nucleotide excision repair in eukaryotic cells , 1993, BioEssays : news and reviews in molecular, cellular and developmental biology.

[6]  A. Hartwig,et al.  Cellular damage by ferric nitrilotriacetate and ferric citrate in V79 cells: interrelationship between lipid peroxidation, DNA strand breaks and sister chromatid exchanges. , 1993, Carcinogenesis.

[7]  P. Predki,et al.  Effect of replacement of "zinc finger" zinc on estrogen receptor DNA interactions. , 1992, The Journal of biological chemistry.

[8]  K. Kasprzak.  The role of oxidative damage in metal carcinogenicity. , 1991, Chemical research in toxicology.

[9]  H. Thiesen,et al.  Transition metals modulate DNA-protein interactions of SP1 zinc finger domains with its cognate target site. , 1991, Biochemical and biophysical research communications.

[10]  A. Yasui,et al.  Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain , 1990, Nature.

[11]  Max Costa,et al.  Studies on the mechanism of nickel‐induced heterochromatin damage; effect on specific DNA‐protein interactions , 1989 .

[12]  N. T. Christie.  The synergistic interaction of Nickel(II) with dna damaging agents , 1989 .

[13]  F W Sunderman,et al.  Mechanistic aspects of nickel carcinogenicity. , 1989, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[14]  A. Hartwig,et al.  Enhancement of UV-induced mutagenesis and sister-chromatid exchanges by nickel ions in V79 cells: evidence for inhibition of DNA repair. , 1989, Mutation research.

[15]  X. W. Wang,et al.  Effect of magnesium on nickel-induced genotoxicity and cell transformation. , 1987, Carcinogenesis.

[16]  J. Lavelle,et al.  Nickel(II) genotoxicity: potentiation of mutagenesis of simple alkylating agents. , 1986, Mutation research.

[17]  L. Poirier,et al.  Antagonism by essential divalent metals and amino acids of nickel(II)-DNA binding in vitro. , 1986, Toxicology and applied pharmacology.

[18]  J. Basilion,et al.  Preferential DNA-protein cross-linking by NiCl2 in magnesium-insoluble regions of fractionated Chinese hamster ovary cell chromatin. , 1985, Cancer research.

[19]  S. Boiteux,et al.  The Escherichia coli O6-methylguanine-DNA methyltransferase does not repair promutagenic O6-methylguanine residues when present in Z-DNA. , 1985, The Journal of biological chemistry.

[20]  C. Haipek,et al.  (6-4)Photoproducts are removed from the DNA of UV-irradiated mammalian cells more efficiently than cyclobutane pyrimidine dimers. , 1985, Mutation research.

[21]  M. Costa,et al.  Induction of chromosomal damage in Chinese hamster ovary cells by soluble and particulate nickel compounds: preferential fragmentation of the heterochromatic long arm of the X-chromosome by carcinogenic crystalline NiS particles. , 1985, Cancer research.

[22]  M. Mr..  The relation of three-dimensional DNA structure to DNA repair as studied by nucleoid sedimentation. , 1984 .

[23]  M. Mattern.  The relation of three-dimensional DNA structure to DNA repair as studied by nucleoid sedimentation. , 1984, Nucleic acids symposium series.

[24]  D. Swartzendruber,et al.  Toxic metals produce an S-phase-specific cell cycle block. , 1982, Research communications in chemical pathology and pharmacology.

[25]  D. Swartzendruber,et al.  Comparison of protein, RNA, and DNA binding and cell-cycle-specific growth inhibitory effects of nickel compounds in cultured cells. , 1982, Toxicology and applied pharmacology.

[26]  Y. Nakabeppu,et al.  Purification and characterization of normal and mutant forms of T4 endonuclease V. , 1982, The Journal of biological chemistry.

[27]  S. Robison,et al.  The induction of DNA strand breakage by nickel compounds in cultured Chinese hamster ovary cells. , 1982, Cancer letters.

[28]  S. Paillet,et al.  Induction of trifluorothymidine-resistant mutants by metal ions in L5178Y/TK+/- cells. , 1980, Mutation research.

[29]  T. Sanner,et al.  Synergistic effect on morphological transformation of hamster embryo cells by nickel sulphate and benz[a]pyrene. , 1980, Cancer letters.

[30]  M. Miyaki,et al.  Mutagenicity of metal cations in cultured cells from Chinese hamster. , 1979, Mutation research.

[31]  T. Kunkel,et al.  On the fidelity of DNA replication. , 1979, Cold Spring Harbor symposia on quantitative biology.

[32]  R. Johnson,et al.  Ultraviolet-induced DNA excision repair in human B and T lymphocytes. II. Effect of inhibitors and DNA precursors. , 1979, Biochimica et biophysica acta.

[33]  P. Cook,et al.  Detection and repair of single-strand breaks in nuclear DNA , 1976, Nature.

[34]  L. Loeb,et al.  Metal activation of DNA synthesis. , 1976, Biochemical and biophysical research communications.

[35]  lARe Monograhs.  Nickel and nickel compounds. , 1976, IARC monographs on the evaluation of the carcinogenic risk of chemicals to man.

[36]  P. Cook,et al.  Supercoils in human DNA. , 1975, Journal of cell science.

[37]  J. Higginson,et al.  International Agency for Research on Cancer. , 1968, WHO chronicle.

[38]  Ernest,et al.  Enzymatic synthesis of deoxyribonucleic acid. , 1969, Harvey lectures.

[39]  D. Mazia,et al.  THE PARTICULATE ORGANIZATION OF THE CHROMOSOME. , 1954, Proceedings of the National Academy of Sciences of the United States of America.