Genotoxic Effects of Metal Compounds
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).
Unable to display preview. Download preview PDF.
- 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
- 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
- DFG (1992) Maximale Arbeitsplatzkonzentrationen und Biologische Arbeitsstoff-Toleranzwerte. VCH, WeinheimGoogle Scholar
- 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
- 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
- Hartwig A (1993) Role of DNA repair inhibition in lead- and cadmium-induced genotoxicity: A review. Environ. Health Persp., in pressGoogle Scholar
- Hartwig A, Beyersmann D (1993) mechanisms in metal genotoxicity: The significance of interactions with DNA repair. Toxicol. Letters, in pressGoogle Scholar
- 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
- 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
- IARC (1980) Some metals and metal compounds. IARC Monographs. Vol. 23. International Agency for Research on Cancer, LyonGoogle Scholar
- IARC (1990) Chromium, nickel and welding. IARC monographs Vol. 49. International Agency for Research on Cancer, LyonGoogle Scholar
- IARC (1993) Cadmium and cadmium compounds. IARC monographs. International Agency for Research on Cancer, Lyon, in printGoogle Scholar