Skip to main content
SpringerLink
Log in

Current aspects in metal genotoxicity

  • Mini-review
  • Published:
Biometals Aims and scope Submit manuscript

Abstract

While carcinogenic metal ions are mostly non-mutagenic in bacteria, different types of cellular damage have been observed in mammalian cells, which may account for their carcinogenic potential. Two modes of action seem to be predominant: the induction of oxidative DNA damage, best established for chromium compounds, and the interaction with DNA repair processes, leading to an enhancement of genotoxicity in combination with a variety of DNA damaging agents. In the case of Cd(II), Ni(II), Co(II), Pb(II) and As(III), DNA repair processes are disturbed at low, non-cytotoxic concentrations of the respective metal compounds. Even though different steps in DNA repair are affected by the diverse metals, one common mechanism might be the competition with essential metal ions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amacher DE, Paillet SC. 1980 Induction of trifluorothymidine-resistant mutants by metal ions in L5178Y/TK+/- cells. Mutat Res 78, 279–288.

    Google Scholar 

  • Bates MN, Smith AH, Hopenhayn-Rich C. 1992 Arsenic ingestion and internal cancers: a review. Am J Epidemiol 135, 462–476.

    Google Scholar 

  • Beyersmann D, Hartwig A. 1992 The genetic toxicology of cobalt. Toxicol Appl Pharmacol 115, 137–145.

    Google Scholar 

  • Beyersmann D, Hechtenberg S, Block C, Kirchherr H. 1992 Interactions of cadmium with cellular signal transduction. In: Merian E, Haerdi W, eds. Metal Compounds in Environment and Life 4. Science and Technology Letters, Northwood: 187–192.

    Google Scholar 

  • Chao CCK, Huang C-L. 1993 Inhibition of UV-damaged DNA recognition activity in HeLa cells by calcium ionophore A23187: potential involvement of cytosolic proteins. Biochem Biophys Res Commun 193, 764–770.

    Google Scholar 

  • Chin Ye, Snow ET, Christie NT. 1994 The stimulatory effect of nickel chloride on DNA replication in human HeLa cells and Escherichia coli. Carcinogenesis 15, 1013–1016.

    Google Scholar 

  • Christie NT. 1989 The synergistic interaction of nickel(II) with DNA damaging agents. Toxicol Environ Chem 22, 51–59.

    Google Scholar 

  • Cohen AD, Kargacin B, Klein CB, Costa M. 1993 Mechanisms of chromium carcinogenicity and toxicity. Crit Rev Toxicol 23, 255–281.

    Google Scholar 

  • Dubins JS, La Velle M. 1986 Nickel(II) genotoxicity: potentiation of mutagenesis of simple alkylating agents. Mutat Res 162, 187–199.

    Google Scholar 

  • Ebina Y, Okada S, Hamazaki S, Ogino F, Li J-I, Midorikawa O. 1986 Nephrotoxicity and renal cell carcinoma after use of iron- and aluminium-nitrilotriacetate complexes in rats. J Natl Cancer Inst 76, 107–113.

    Google Scholar 

  • Gebhart E, Rossman TG. 1991 Mutagenicity, carcinogenicity and teratogenicity. In Merian E, ed. Metals and their Compounds in the Environment, Weinheim: VCH Verlagsgesellschaft; 617–640.

    Google Scholar 

  • Goldman M, Dacre JC. 1991 Inorganic arsenic compounds: are they carcinogenic, mutagenic, teratogenic? Environ Geochem Health 13, 179–191.

    Google Scholar 

  • Halliwell B, Gutteridge JMC. 1990 Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186, 1–85.

    Google Scholar 

  • Hartwig A. 1994 Role of DNA repair inhibition in lead- and cadmium-induced genotoxicity: a review. Environ Health Perspect, in press.

  • Hartwig A, Beyersmann D. 1989a Enhancement of UV-induced mutagenesis and sister-chromatid exchanges by nickel ions in V79 cells: evidence for inhibition of DNA repair. Mutat Res 217, 65–73.

    Google Scholar 

  • Hartwig A, Beyersmann D. 1989b Comutagenicity and inhibition of DNA repair by metal ions in mammalian cells. Biol Trace Element Res 21, 359–365.

    Google Scholar 

  • Hartwig A, Kasten U, Boakye-Dankwa K, Schlepegrell R, Beyersmann D. 1990a Uptake and genotoxicity of micromolar concentrations of cobalt chloride in mammalian cells. Toxicol Environ Chem 28, 205–215.

    Google Scholar 

  • Hartwig A, Schlepegrell R, Beyersmann D. 1990b Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells. Mutat Res 241, 75–82.

    Article  CAS  PubMed  Google Scholar 

  • Hartwig A, Snyder RD, Schlepegrell R, Beyersmann D. 1991 Modulation by Co(II) of UV-induced DNA repair, mutagenesis and sister-chromatid exchanges in mammalian cells. Mutat Res 248, 177–185.

    Google Scholar 

  • Hartwig A, Klyszcz-Nasko H, Schlepegrell R, Beyersmann D. 1993 Cellular damage by ferric nitrilotriacetate and ferric citrate in V79 cells: interrelationship between lipid peroxidation, DNA strand breaks and sister-chromatid exchanges. Carcinogenesis 14, 107–112.

    Google Scholar 

  • Hartwig A, Krüger I, Beyersmann D. 1994a Mechanisms in nickel genotoxicity: the significance of interactions with DNA repair. Toxicol Lett 72, 353–358.

    Google Scholar 

  • Hartwig A, Mullenders LHF, Schlepegrell R, Kasten U, Beyersmann D. 1994b Nickel(II) interferes with the incision step in nucleotide excision repair in mammalian cells. Cancer Res 54, 4045–4051.

    Google Scholar 

  • Higinbotham KG, Rice JM, Diwan BA, Kasprzak KS, Reed CD, Perantoni AO. 1992 GGT to GTT transversions in codon 12 of the K-ras oncogene in rat renal sarcomas induced with nickel subsulfide of nickel subsulfide/iron are consistent with oxidative damage to DNA. Cancer Res 52, 4747–4751.

    Google Scholar 

  • Huang H, Huang CF, Huang JS, Wang TC, Jan KY. 1992 The transition from late g1 to early S phase is most vulnerable to the co-clastogenic effect of ultraviolet irradiation plus arsenite. Int J Radiat Biol61, 57–62.

    Google Scholar 

  • Inoue T, Ohta Y, Sadaie Y, Kada T. 1981 Effect of cobaltous chloride on spontaneous mutation induction in a Bacillus subtilis mutator strain. Mutat Res 91, 41–45.

    Google Scholar 

  • IARC 1980 Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. 23: Some Metals and Metallic Compounds. Lyon: IARC.

    Google Scholar 

  • IARC 1987 Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Supplement 7. Lyon: IARC.

    Google Scholar 

  • IARC 1990 Monographs on the Evaluation of the Carcinogenic Risks to Humans, Vol. 49: Chromium, Nickel and Welding. Lyon: IARC.

    Google Scholar 

  • IARC 1991 Monographs on the Evaluation of the Carcinogenic Risks to Humans, Vol. 52: Chlorinated Drinking Water; Chlorination By-Products; some other Haloginated Compounds; Cobalt and Cobalt Compounds. Lyon: IARC.

    Google Scholar 

  • IARC 1993 Monographs on the Evaluation of the Carcinogenic Risks to Humans, Vol. 58: Beryllium, Cadmium, Mercury, and Exposures in the Glass Manufacturing Industry. Lyon: IARC.

    Google Scholar 

  • Jacobson-Kram D, Montalbano D. 1985 The reproductive effects assessment group's report on the mutagenicity of inorganic arsenic. Environ Mutagen 7, 787–804.

    Google Scholar 

  • Jha AN, Noditi M, Nilsson R, Natarajan AT. 1992 Genotoxic effects of sodium arsenite on human cells. Mutat Res 284, 215–221.

    Google Scholar 

  • Kada T, Kanematsu N. 1978 Reduction of N-methyl-N'-nitro-N-nitrosoguanidine-induced mutations by cobalt chloride in Escherichia coli. Proc Japan Acad 4B, 234–237.

    Google Scholar 

  • Kada T, Inoue T, Ohta T, Shirasu Y. 1986 Antimutagens and their modes of action. In: Shankel DM, Hartman PE, Kada T, Hollaender A, eds. Antimutagenesis and Anticarcinogenesis Mechanisms. New York: Plenum: 181–196.

    Google Scholar 

  • Kasprzak KS. 1991 The role of oxidative damage in metal carcinogenicity. Chem Res Toxicol 4, 604–615.

    Google Scholar 

  • Kasprzak KS, Diwan B, Konishi N, Misra M, Rice JM. 1990 Initiation by nickel acetate and promotion by sodium barbital of renal cortical epithelial tumors in male F344 rates. Carcinogenesis 11, 647–652.

    Google Scholar 

  • Lee-Chen SF, Yu CT, Jan KY. 1992 Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells. Mutagenesis 7, 51–55.

    Google Scholar 

  • Lee T-C, Huang RY, Jan KY. 1985 Sodium arsenite enhances the cytotoxicity, clastogenicity, and 6-thioguanine-resistant mutagenicity of ultraviolet light in Chinese hamster ovary cells. Mutat Res 148, 83–89.

    Google Scholar 

  • Lee T-C, Wang-Wuu S, Huang RY, Lee KC, Jan KY. 1986a Differential effects of pre-and posttreatment of sodium arsenite on the genotoxicity of methyl methansulfonate in Chinese hamster ovary cells. Cancer Res 46, 1854–1857.

    Google Scholar 

  • Lee T-C, Lee KC, Tzeng YJ, Huang RY, Jan KY. 1986b Sodium arsenite potentiates the clastogenicity and mutagenicity of DNA crosslinking agents. Environ Mutagen 8, 119–128.

    Google Scholar 

  • Leitão AC, Soares RA, Cardoso JS, Guillobel HC, Caldas LR. 1993 Inhibition and induction of SOS responses in Escherichia coli by cobaltous chloride. Mutat Res 286, 173–180.

    Google Scholar 

  • Léonard A, Lauwerys R. 1990 Mutagenicity, carcinogenicity and teratogenicity of cobalt metal and cobalt compounds. Mutat Res 239, 17–27.

    Google Scholar 

  • Li JH, Rossman TG. 1989a Mechanisms of comutagenesis of sodium arsenite with N-methyl-N-nitrosourea. Biol Trace Element Res 21, 373–381.

    Google Scholar 

  • Li JH. Rossman TG. 1989b Inhibition of DNA ligase activity by arsenite: A possible mechanism of its comutagenesis. Mol Toxicol 2, 1–9.

    Google Scholar 

  • Livneh Z. 1986 Mechanism of replication of UV-irradiatcd single-stranded DNA by DNA polymerase III holoenzyme of Escherichia coli: Implications for SOS-mutagenesis. J Biol Chem 261, 9526–9533.

    Google Scholar 

  • Mandel R, Ryser HJ-P. 1984 Mutagenicity of cadmium in Salmonella typhimurium and its synergism with two nitrosamines. Mutat Res 138, 9–16.

    Google Scholar 

  • Mandel R, Ryser HJ-P. 1987 Mechanisms of synergism in the mutagenicity of cadmium and N'-methyl-N' nitrosourea in Salmonella typhimurium: the effect of pH. Mutation Res 176, 1–10.

    Google Scholar 

  • Nagaoka M, Kuwahara J, Sugiura Y. 1993 Alteration of DNA binding specificity by nickel(II) substitution in three zinc(II) fingers of transcription factor SP1. Biochem Biophys Res Commun 194, 1515–1520.

    Google Scholar 

  • Nakatsuka S, Tanaka H, Namba M. 1990 Mutagenic effects of ferric nitrilotriacetate (Fe-NTA) on V79 Chinese hamster cells and its inhibitory effects on cell-cell communication. Carcinogenesis 11, 257–260.

    Google Scholar 

  • Nocentini S. 1987 Inhibition of DNA replication and repair by cadmium in mammalian cells. Protective interaction of zinc. Nucleic Acids Res 15, 4211–4225.

    Google Scholar 

  • Okui T, Fujiwara Y. 1986 Inhibition of human excision DNA repair by inorganic arsenic and the co-mutagenic effect in V79 Chinese hamster cells. Mutat Res 172, 69–76.

    Google Scholar 

  • Oldiges H, Takenaka S, Oberdoerster G, Hochrainer D, König H. 1984 Lung carcinomas in rats after low level cadmium inhalation. Toxicol Environ Chem 9, 41–51.

    Google Scholar 

  • Oldiges H, Hochrainer D, Glaser U. 1989 Long-term inhalation study with Wistar rats and four cadmium compounds. Toxicol Environ Chem 19, 217–222.

    Google Scholar 

  • Pagano DA, Zeiger E. 1992 Conditions for detecting the mutagenicity of divalent metals in Salmonella typhimurium. Environ Mol Mutagen 19, 139–146.

    Google Scholar 

  • Predki PF, Sarkar B. 1992 Effect of replacement of ‘zinc finger’ zinc on estrogen receptor DNA interactions. J Biol Chem 267. 5842–5846.

    Google Scholar 

  • Rivedal E, Sanner T. 1980 Synergistic effect on morphological transformation of hamster embryo cells by nickel sulfate and benz(a)pyrene. Cancer Lett 8, 203–208.

    Google Scholar 

  • Rivedal E Sanner T. 1981 Metal salts as promoters of in vitro morphological transformation of hamster embryo cells initiated by benzo(a)pyrene. Cancer Res 41, 2950–2953.

    Google Scholar 

  • Rossman TG 1981 Enhancement of UV-mutagenesis by low concentrations of arsenite in E. coli. Mutat Res 91, 207–211.

    Google Scholar 

  • Rossman TG, Molina M. 1986 The genetic toxicology of metal compounds: II. Enhancement of ultraviolet light-induced mutagenesis in E. coli WP2. Environ Mutagen 8, 263–271.

    Google Scholar 

  • Roy NK Rossman TG 1992 Mutagenesis and comutagenesis by lead compounds. Mutat Res 298, 97–103.

    Google Scholar 

  • Sirover MA, Loeb LA. 1976 Metal activation of DNA synthesis. Biochem Biophys Res Commun 70, 812–817.

    Google Scholar 

  • Sirover MA, Loeb LA. 1977 On the fidelity of DNA replication. J Biol Chem 252, 3605–3610.

    Google Scholar 

  • Snyder RD, Davis GF, Lachmann PJ. 1989 Inhibition by metals of X-ray and ultraviolet-induced DNA repair in human cells. Biol Trace Element Res 21, 389–398.

    Google Scholar 

  • Stayner L, Smith RS, Thun M, Schnorr T, Lemen RA. 1992 Dose-response analysis and quantitative assessment of lung cancer risk and occupational cadmium exposure. Ann Epidemiol 2, 177–194.

    Google Scholar 

  • Takahashi K, Imaeda T, Kawazoe Y. 1988 Effect of metal ions on the adaptive response induced by N-methyl-N-nitrosourea in Escherichia coli. Biochim Biophys Res Commun 157, 1124–1130.

    Google Scholar 

  • Takahashi K, Suzuki M, Sekiguchi M, Kawazoe Y. 1992 Effect of metal ions on transcription of the ada gene which encodes O 6-methylguanine-DNA-methyltransferase of Escherichia coli. Chem Pharm Bull 40, 2483–2486.

    Google Scholar 

  • Tanaka K, Miura N, Satokata I, et al. 1990 Analysis of a human DNA excision repair gene involved in group A Xeroderma pigmentosum and containing a zinc-finger domain. Nature 348, 73–76.

    Google Scholar 

  • Tkeshelashvili LK, Reid TM, McBride J, Loeb LA. 1993 Nickel induces a signature mutation for oxygen free radical damage. Cancer Res 53, 4172–4174.

    Google Scholar 

  • Toyokuni S, Sagripanti J-L. 1993 Induction of oxidative singleand double-strand breaks in DNA by ferric citrate. Free Rad Biol Med 15, 117–123.

    Google Scholar 

  • Umemura T, Sai K, Takagi A, Hasegawa R, Kurokawa Y. 1990 Formation of 8-hydroxyguanosine (8-OH-dG) in rat kidney DNA after intraperitoneal administration of ferric nitrilotriacetate (Fe-NTA). Carcinogenesis 11, 345–347.

    Google Scholar 

  • Wang XW, Lin X, Klein CB, Bhamra RK, Lee YW, Costa M. 1992 A conserved region in human and Chinese hamster X chromosomes can induce cellular senescence of nickel-transformed Chinese hamster cell lines. Carcinogenesis 13, 555–561.

    Google Scholar 

  • Yamada H, Miyahara T, Sasaki YF. 1993 Inorganic cadmium increases the frequency of chemically induced chromosome aberrations in cultured mammalian cells. Mutat Res 302, 137–145.

    Google Scholar 

  • Yang JL, Chen M-F, Wu C-W, Lee T-C. 1992 Posttreatment with sodium arsenite alters the mutational spectrum induced by ultraviolet light irradiation in Chinese hamster ovary cells. Environ Mol Mutagen 20, 156–164.

    Google Scholar 

  • Yokoiyama A, Kada T, Kuroda Y. 1990 Antimutagenic action of cobaltous chloride on radiation-induced mutations in cultured Chinese hamster cells. Mutat Res 245, 99–105.

    Google Scholar 

  • Zelikoff JT, Li JH, Hartwig A, Wang XW, Costa M, Rossman TG. 1988 Genetic toxicology of lead compounds. Carcinogenesis 9. 1727–1732.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology and Chemistry, University of Bremen, Bremen, Germany

    Andrea Hartwig

Authors
  1. Andrea Hartwig
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hartwig, A. Current aspects in metal genotoxicity. Biometals 8, 3–11 (1995). https://doi.org/10.1007/BF00156151

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00156151

Keywords

Search

Navigation