Genotoxic Effects of Metal Compounds

  • D. Beyersmann
  • A. Hartwig
Conference paper
Part of the Archives of Toxicology, Supplement 16 book series (TOXICOLOGY, volume 16)


Genotoxic effects are important indicators of carcinogenicity. The International Agency for Research on Cancer has classified compounds of arsenic, chromium (VI), nickel and cadmium as carcinogenic to humans (IARC 1980, 1990, 1993). Based on animal data, the German Science Foundation (DFG) also has classified antimony trioxide, beryllium and cobalt as mammalian carcinogens (DFG 1992). In addition, certain metals further the generation of tumors in animals depending on their chemical form and route of administration (Sunderman 1984; Lauwerys 1989; Magos 1991). Regarding the potential risk to human by airborn carcinogens, a German Government Commission has ranked seven substances as the most important for the general population. These are (in decreasing order of contribution to the total risk): polycyclic aromatic hydrocarbons, asbestos, benzene and four metals, i.e. chromium, arsenic, cadmium and nickel. The carcinogenic potential of metals is highly dependent on their speciation. Only the chromates (with chromium in its hexavalent state) but not Cr(III) compounds are carcinogens, since the chromates are able to penetrate cell membranes via anion carriers whereas Cr(III) is not (Jenette 1979). Nickel metal and nickel subsulfide are more efficient carcinogens than nickel chloride, since the soluble nickel ion is taken up slowly. At variance, the soluble CdCl2 is a stronger carcinogen than the weakly soluble CdS, since the soluble ion is better bioavailable (Heinrich et al. 1989). With iron and platinum, only special complexes with enhanced bioavailability are carcinogenic to animals. These include the complexes Fe(III)NTA (Ebina et al. 1986) and cis Pt(II)Cl2(NH3)2 (Leopold et al. 1979).


Genotoxic Effect Metal Compound Inositol Triphosphate German Science Foundation Antimony Trioxide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beyersmann D (1991) The significance of interactions in metal essentiality and toxicity. In Merian E (ed.) Metals and their compounds in the environment. VCH Weinheim, pp. 491–509Google Scholar
  2. Block C, Freyermuth S, Beyersmann D, Maliviya A N (1992) Role of cadmium in activating nuclear protein kinase C and the enzyme binding to nuclear protein. J. Biol. Chem. 267: 19824–19828PubMedGoogle Scholar
  3. Cohen M, Latta D, Coogan T, Costa M (1991) Mechanisms of metal carcinogenesis: The reactions of metals with nucleic acids. In: Foulkes EC (ed) Biological effects of heavy metals. Vol II. CRC Press, Boca Raton, pp. 19–75Google Scholar
  4. DFG (1992) Maximale Arbeitsplatzkonzentrationen und Biologische Arbeitsstoff-Toleranzwerte. VCH, WeinheimGoogle Scholar
  5. Ebina Y, Hamazaki S, Li J L, Midorikawa O, Ogino F, Okada S (1986): Nephrotoxicity and renal cell carcinoma after use of iron- and aluminium-nitriloacetate complexes in rats. J. Ntl. Cancer Inst. 76:107–113Google Scholar
  6. Furst A (1987) Metal interactions in carcinogenesis. In: Fishbein L, Furst A, Mehlman MA (eds) Genotoxic and carcinogenic metals: Environmental and occupational occurrence and exposure. Princeton Publishing Co., Princeton, pp 279–293Google Scholar
  7. Hartwig A (1993) Role of DNA repair inhibition in lead- and cadmium-induced genotoxicity: A review. Environ. Health Persp., in pressGoogle Scholar
  8. Hartwig A, Beyersmann D (1993) mechanisms in metal genotoxicity: The significance of interactions with DNA repair. Toxicol. Letters, in pressGoogle Scholar
  9. Hartwig A, Schlepegrell R, Beyersmann D (1990) Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells. Mutat. Res. 241:75–82PubMedCrossRefGoogle Scholar
  10. Hartwig A, Snyder R D, Schlepegrell R, Beyersmann D (1991a) Modulation by Co(II) of UV-induced DNA repair, mutagenesis and sister-chromatid exchanges in mammalian cells. Mutat. Res. 248:177–185CrossRefGoogle Scholar
  11. Hartwig A, Schlepegrell R, Beyersmann D (1991b) Interactions in nickel mutagenicity: Indirect mechanisms in genotoxicity and interference with DNA repair In: Merian E, Haerdi W (eds) Metal Compounds in Environment and Life 4: Science Reviews, Wilmington, pp 475–480Google Scholar
  12. 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: 107–112PubMedCrossRefGoogle Scholar
  13. Hechtenberg S, and Beyersmann D (1991) Inhibition of sarcoplasmic reticulum Ca2+ ATPase activity by cadmium, lead and mercury. Enzyme 45:109–115PubMedGoogle Scholar
  14. Heinrich U, Peters L, Ernst H, Rittinghause S, Dasenbrock C, König H (1989) Investigation on the carcinogenic effects of various cadmium compounds after inhalation exposure in hamsters and mice. Exper. Pathol. 37:1–4Google Scholar
  15. IARC (1980) Some metals and metal compounds. IARC Monographs. Vol. 23. International Agency for Research on Cancer, LyonGoogle Scholar
  16. IARC (1990) Chromium, nickel and welding. IARC monographs Vol. 49. International Agency for Research on Cancer, LyonGoogle Scholar
  17. IARC (1993) Cadmium and cadmium compounds. IARC monographs. International Agency for Research on Cancer, Lyon, in printGoogle Scholar
  18. Jenette KE (1979) Chromate metabolism in liver microsomes. Biol. Trace Elem. Res. 1: 55–62CrossRefGoogle Scholar
  19. Jin P. Ringertz N R (1990) Cadmium induces transcription of proto-oncogenes c-jun and c-myc in rat L6 myoblasts. J. Biol. Chem. 265:14061–14064PubMedGoogle Scholar
  20. Kasprzak K (1991) The role of oxidative damage in metal carcinogenicity. Chem. Res. Toxicol. 4: 604–615PubMedCrossRefGoogle Scholar
  21. Klein C B, Frenkel K, and Costa M (1991) The role of oxidative processes in metal carcinogenesis. Chem. Res. Toxicol. 4: 592–604PubMedCrossRefGoogle Scholar
  22. Kortenkamp A, Ozolins Z, Beyermann D, O’Brien P (1989) Generation of PM2 DNA breaks in the course of reduction of chromium(VI) by glutathione. Mutat. Res. 216:19–26PubMedGoogle Scholar
  23. Lauwerys R R (1989) Metals — Epidemiological and experimental evidence for carcinogenicity. Arch. Toxicol. Suppl. 13: 21–27PubMedGoogle Scholar
  24. Leopold W R, Miller E C, Miller J A (1979) Carcinogenicity of antitumor cis-platinum(II) complexes in the mouse and rat. Cancer Res. 39: 913–918PubMedGoogle Scholar
  25. Lohmann R D, Beyersmann D (1993) Cadmium and zinc mediated changes of the Ca2+-dependent endonuclease in apoptosis. Biochem. Biophys. Res. Commun. 190: 1097–1103PubMedCrossRefGoogle Scholar
  26. Magos L (1991) Epidemiological and experimental aspects of metal carcinogenesis: Physicochemical properties, kinetics, and the active species. Environ. Health Perspect. 95:157–189PubMedCrossRefGoogle Scholar
  27. 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: 257–260PubMedCrossRefGoogle Scholar
  28. Rossi A, Manzo L, Orrenius S, Vahter M, Nicotera P (1991) Modifications of cell signalling in the cytotoxicity of metals. Pharmacology Toxicology 68:424–429PubMedCrossRefGoogle Scholar
  29. Sirover M A, and Loeb L A (1976) Infidelity of DNA synthesis in vitro: Screening for potential metal mutagens or carcinogens. Science 194:1434–1436PubMedCrossRefGoogle Scholar
  30. Smith J B, Dwyer S D, Smith L (1989) Cadmium evokes inositol polyphosphate formation and calcium mobilization. J. Biol. Chem. 264: 7115–7118PubMedGoogle Scholar
  31. Sunderman F W, Jr. (1984) Recent advances in metal carcinogenesis. Ann. Clin. Lab. Sci. 14: 93–122PubMedGoogle Scholar
  32. Sunderman F W, Jr., Barber A M (1988) Fingerloops, oncogenes and metals. Ann. Clin. Lab. Sci. 18:267–288PubMedGoogle Scholar
  33. Tkeshelashvili L K, Shearman C W, Zakour R A, Koplitz R M, and Loeb L A (1980) Effects of arsenic, selenium and chromium on the fidelity of DNA Synthesis. Cancer Res. 40: 2455–2460PubMedGoogle Scholar
  34. Zhang G H, Yamaguchi M, Kimura S, Higham S, and Kraus-Friedman N (1990) Effects of heavy metals on rat liver microsomal Ca2+ ATPase and Ca2+ sequestering. J. Biol. Chem. 265:2184–2189PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • D. Beyersmann
    • 1
  • A. Hartwig
    • 1
  1. 1.Department of Biology and ChemistryUniversity of BremenBremenGermany

Personalised recommendations