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. 2001 Oct;58(10):619–625. doi: 10.1136/oem.58.10.619

Update on the genotoxicity and carcinogenicity of cobalt compounds

D Lison 1, M De Boeck 1, V Verougstraete 1, M Kirsch-Volders 1
PMCID: PMC1740056  PMID: 11555681

Abstract

OBJECTIVE—To integrate recent understandings of the mechanisms of genotoxicity and carcinogenicity of the different cobalt compounds.
METHOD—A narrative review of the studies published since the last IARC assessment in 1991 (genotoxicity, experimental carcinogenesis, and epidemiology).
RESULTS—Two different mechanisms of genotoxicity, DNA breakage induced by cobalt metal and especially hard metal particles, and inhibition of DNA repair by cobalt (II) ions contribute to the carcinogenic potential of cobalt compounds. There is evidence that soluble cobalt (II) cations exert a genotoxic and carcinogenic activity in vitro and in vivo in experimental systems but evidence in humans is lacking. Experimental data indicate some evidence of a genotoxic potential for cobalt metal in vitro in human lymphocytes but there is no evidence available of a carcinogenic potential. There is evidence that hard metal particles exert a genotoxic and carcinogenic activity in vitro and in human studies, respectively. There is insufficient information for cobalt oxides and other compounds.
CONCLUSION—Although many areas of uncertainty remain, an assessment of the carcinogenicity of cobalt and its compounds requires a clear distinction between the different compounds of the element and needs to take into account the different mechanisms involved.


Keywords: cobalt; DNA breakage; inhibition of DNA repair

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Selected References

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  1. Anard D., Kirsch-Volders M., Elhajouji A., Belpaeme K., Lison D. In vitro genotoxic effects of hard metal particles assessed by alkaline single cell gel and elution assays. Carcinogenesis. 1997 Jan;18(1):177–184. doi: 10.1093/carcin/18.1.177. [DOI] [PubMed] [Google Scholar]
  2. Asmuss M., Mullenders L. H., Hartwig A. Interference by toxic metal compounds with isolated zinc finger DNA repair proteins. Toxicol Lett. 2000 Mar 15;112-113:227–231. doi: 10.1016/s0378-4274(99)00273-8. [DOI] [PubMed] [Google Scholar]
  3. Borm P. J., Driscoll K. Particles, inflammation and respiratory tract carcinogenesis. Toxicol Lett. 1996 Nov;88(1-3):109–113. doi: 10.1016/0378-4274(96)03725-3. [DOI] [PubMed] [Google Scholar]
  4. Bucher J. R., Hailey J. R., Roycroft J. R., Haseman J. K., Sills R. C., Grumbein S. L., Mellick P. W., Chou B. J. Inhalation toxicity and carcinogenicity studies of cobalt sulfate. Toxicol Sci. 1999 May;49(1):56–67. doi: 10.1093/toxsci/49.1.56. [DOI] [PubMed] [Google Scholar]
  5. De Boeck M., Lardau S., Buchet J. P., Kirsch-Volders M., Lison D. Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt-containing dust: a cross-sectional study. Environ Mol Mutagen. 2000;36(2):151–160. doi: 10.1002/1098-2280(2000)36:2<151::aid-em10>3.3.co;2-m. [DOI] [PubMed] [Google Scholar]
  6. De Boeck M., Lison D., Kirsch-Volders M. Evaluation of the in vitro direct and indirect genotoxic effects of cobalt compounds using the alkaline comet assay. Influence of interdonor and interexperimental variability. Carcinogenesis. 1998 Nov;19(11):2021–2029. doi: 10.1093/carcin/19.11.2021. [DOI] [PubMed] [Google Scholar]
  7. GOLDWASSER E., JACOBSON L. O., FRIED W., PLZAK L. F. Studies on erythropoiesis. V. The effect of cobalt on the production of erythropoietin. Blood. 1958 Jan;13(1):55–60. [PubMed] [Google Scholar]
  8. Hagmar L., Bonassi S., Strömberg U., Brøgger A., Knudsen L. E., Norppa H., Reuterwall C. Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res. 1998 Sep 15;58(18):4117–4121. [PubMed] [Google Scholar]
  9. Hartwig A., Snyder R. D., Schlepegrell R., Beyersmann D. Modulation by Co(II) of UV-induced DNA repair, mutagenesis and sister-chromatid exchanges in mammalian cells. Mutat Res. 1991 May;248(1):177–185. doi: 10.1016/0027-5107(91)90099-a. [DOI] [PubMed] [Google Scholar]
  10. Kasprzak K. S., Zastawny T. H., North S. L., Riggs C. W., Diwan B. A., Rice J. M., Dizdaroglu M. Oxidative DNA base damage in renal, hepatic, and pulmonary chromatin of rats after intraperitoneal injection of cobalt(II) acetate. Chem Res Toxicol. 1994 May-Jun;7(3):329–335. doi: 10.1021/tx00039a009. [DOI] [PubMed] [Google Scholar]
  11. Kasten U., Mullenders L. H., Hartwig A. Cobalt(II) inhibits the incision and the polymerization step of nucleotide excision repair in human fibroblasts. Mutat Res. 1997 Jan 31;383(1):81–89. doi: 10.1016/s0921-8777(96)00052-3. [DOI] [PubMed] [Google Scholar]
  12. Kawanishi S., Inoue S., Yamamoto K. Active oxygen species in DNA damage induced by carcinogenic metal compounds. Environ Health Perspect. 1994 Sep;102 (Suppl 3):17–20. doi: 10.1289/ehp.94102s317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lasfargues G., Wild P., Moulin J. J., Hammon B., Rosmorduc B., Rondeau du Noyer C., Lavandier M., Moline J. Lung cancer mortality in a French cohort of hard-metal workers. Am J Ind Med. 1994 Nov;26(5):585–595. doi: 10.1002/ajim.4700260502. [DOI] [PubMed] [Google Scholar]
  14. Lewis C. G., Belniak R. M., Plowman M. C., Hopfer S. M., Knight J. A., Sunderman F. W., Jr Intraarticular carcinogenesis bioassays of CoCrMo and TiAlV alloys in rats. J Arthroplasty. 1995 Feb;10(1):75–82. doi: 10.1016/s0883-5403(05)80103-2. [DOI] [PubMed] [Google Scholar]
  15. Linnainmaa M., Kiilunen M. Urinary cobalt as a measure of exposure in the wet sharpening of hard metal and stellite blades. Int Arch Occup Environ Health. 1997;69(3):193–200. doi: 10.1007/s004200050136. [DOI] [PubMed] [Google Scholar]
  16. Lison D., Carbonnelle P., Mollo L., Lauwerys R., Fubini B. Physicochemical mechanism of the interaction between cobalt metal and carbide particles to generate toxic activated oxygen species. Chem Res Toxicol. 1995 Jun;8(4):600–606. doi: 10.1021/tx00046a015. [DOI] [PubMed] [Google Scholar]
  17. Lison D. Human toxicity of cobalt-containing dust and experimental studies on the mechanism of interstitial lung disease (hard metal disease). Crit Rev Toxicol. 1996 Nov;26(6):585–616. doi: 10.3109/10408449609037478. [DOI] [PubMed] [Google Scholar]
  18. Lison D., Lauwerys R. Study of the mechanism responsible for the elective toxicity of tungsten carbide-cobalt powder toward macrophages. Toxicol Lett. 1992 Apr;60(2):203–210. doi: 10.1016/0378-4274(92)90275-o. [DOI] [PubMed] [Google Scholar]
  19. Lloyd D. R., Phillips D. H., Carmichael P. L. Generation of putative intrastrand cross-links and strand breaks in DNA by transition metal ion-mediated oxygen radical attack. Chem Res Toxicol. 1997 Apr;10(4):393–400. doi: 10.1021/tx960158q. [DOI] [PubMed] [Google Scholar]
  20. Mao Y., Liu K. J., Jiang J. J., Shi X. Generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators in relation to DNA damage and 2'-deoxyguanosine hydroxylation. J Toxicol Environ Health. 1996 Jan;47(1):61–75. doi: 10.1080/009841096161933. [DOI] [PubMed] [Google Scholar]
  21. Merritt K., Brown S. A., Sharkey N. A. The binding of metal salts and corrosion products to cells and proteins in vitro. J Biomed Mater Res. 1984 Nov-Dec;18(9):1005–1015. doi: 10.1002/jbm.820180905. [DOI] [PubMed] [Google Scholar]
  22. Moulin J. J., Wild P., Mur J. M., Fournier-Betz M., Mercier-Gallay M. A mortality study of cobalt production workers: an extension of the follow-up. Am J Ind Med. 1993 Feb;23(2):281–288. doi: 10.1002/ajim.4700230205. [DOI] [PubMed] [Google Scholar]
  23. Moulin J. J., Wild P., Romazini S., Lasfargues G., Peltier A., Bozec C., Deguerry P., Pellet F., Perdrix A. Lung cancer risk in hard-metal workers. Am J Epidemiol. 1998 Aug 1;148(3):241–248. doi: 10.1093/oxfordjournals.aje.a009631. [DOI] [PubMed] [Google Scholar]
  24. Mur J. M., Moulin J. J., Charruyer-Seinerra M. P., Lafitte J. A cohort mortality study among cobalt and sodium workers in an electrochemical plant. Am J Ind Med. 1987;11(1):75–81. doi: 10.1002/ajim.4700110108. [DOI] [PubMed] [Google Scholar]
  25. Méplan C., Richard M. J., Hainaut P. Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells. Oncogene. 2000 Nov 2;19(46):5227–5236. doi: 10.1038/sj.onc.1203907. [DOI] [PubMed] [Google Scholar]
  26. Nackerdien Z., Kasprzak K. S., Rao G., Halliwell B., Dizdaroglu M. Nickel(II)- and cobalt(II)-dependent damage by hydrogen peroxide to the DNA bases in isolated human chromatin. Cancer Res. 1991 Nov 1;51(21):5837–5842. [PubMed] [Google Scholar]
  27. Palecek E., Brázdová M., Cernocká H., Vlk D., Brázda V., Vojtesek B. Effect of transition metals on binding of p53 protein to supercoiled DNA and to consensus sequence in DNA fragments. Oncogene. 1999 Jun 17;18(24):3617–3625. doi: 10.1038/sj.onc.1202710. [DOI] [PubMed] [Google Scholar]
  28. Palit S., Sharma A., Talukder G. Chromosomal aberrations induced by cobaltous chloride in mice in vivo. Biol Trace Elem Res. 1991 May;29(2):139–145. doi: 10.1007/BF03032691. [DOI] [PubMed] [Google Scholar]
  29. Sarkar B. Metal replacement in DNA-binding zinc finger proteins and its relevance to mutagenicity and carcinogenicity through free radical generation. Nutrition. 1995 Sep-Oct;11(5 Suppl):646–649. [PubMed] [Google Scholar]
  30. Suzuki Y., Shimizu H., Nagae Y., Fukumoto M., Okonogi H., Kadokura M. Micronucleus test and erythropoiesis: effect of cobalt on the induction of micronuclei by mutagens. Environ Mol Mutagen. 1993;22(2):101–106. doi: 10.1002/em.2850220208. [DOI] [PubMed] [Google Scholar]
  31. Tüchsen F., Jensen M. V., Villadsen E., Lynge E. Incidence of lung cancer among cobalt-exposed women. Scand J Work Environ Health. 1996 Dec;22(6):444–450. doi: 10.5271/sjweh.166. [DOI] [PubMed] [Google Scholar]
  32. Van Goethem F., Lison D., Kirsch-Volders M. Comparative evaluation of the in vitro micronucleus test and the alkaline single cell gel electrophoresis assay for the detection of DNA damaging agents: genotoxic effects of cobalt powder, tungsten carbide and cobalt-tungsten carbide. Mutat Res. 1997 Aug 1;392(1-2):31–43. doi: 10.1016/s0165-1218(97)00043-8. [DOI] [PubMed] [Google Scholar]
  33. Wild P., Perdrix A., Romazini S., Moulin J. J., Pellet F. Lung cancer mortality in a site producing hard metals. Occup Environ Med. 2000 Aug;57(8):568–573. doi: 10.1136/oem.57.8.568. [DOI] [PMC free article] [PubMed] [Google Scholar]

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