Cobalt and antimony: genotoxicity and carcinogenicity.

The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with DNA repair systems, still need further investigation.

[1]  O. Fardel,et al.  Potassium antimonyl tartrate induces reactive oxygen species-related apoptosis in human myeloid leukemic HL60 cells. , 2002, International journal of oncology.

[2]  A. Hartwig,et al.  The genetic toxicology of cobalt. , 1992, Toxicology and applied pharmacology.

[3]  V. Potkonjak,et al.  Antimoniosis: A particular form of pneumoconiosis , 1983, International archives of occupational and environmental health.

[4]  Ivo Iavicoli,et al.  Genotoxic risk and oxidative DNA damage in workers exposed to antimony trioxide , 2002, Environmental and molecular mutagenesis.

[5]  W. Zou,et al.  Cobalt chloride induces PC12 cells apoptosis through reactive oxygen species and accompanied by AP‐1 activation , 2001, Journal of neuroscience research.

[6]  Xianglin Shi,et al.  Generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators in relation to DNA damage and 2'-deoxyguanosine hydroxylation. , 1996, Journal of toxicology and environmental health.

[7]  J Ashby,et al.  An assessment of the genetic toxicology of antimony trioxide. , 1998, Mutation research.

[8]  D. Sereno,et al.  Antimonial-Mediated DNA Fragmentation inLeishmania infantum Amastigotes , 2001, Antimicrobial Agents and Chemotherapy.

[9]  R. T. Drew,et al.  Subchronic and chronic inhalation toxicity of antimony trioxide in the rat. , 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[10]  P. Wild,et al.  Lung cancer risk in hard-metal workers. , 1998, American journal of epidemiology.

[11]  H. Shimizu,et al.  Micronucleus test and erythropoiesis: Effect of cobalt on the induction of micronuclei by mutagens , 1993, Environmental and molecular mutagenesis.

[12]  Archana Sharma,et al.  Comparison of the clastogenic effects of antimony trioxide on micein vivo following acute and chronic exposure , 2005, Biometals.

[13]  V. Marks,et al.  Fibrosarcomas induced by cobalt chloride (CoCl2) in rats , 1977, Laboratory animals.

[14]  R. Jones Survey of antimony workers: mortality 1961-1992. , 1994, Occupational and environmental medicine.

[15]  P. Borm,et al.  Particles, inflammation and respiratory tract carcinogenesis. , 1996, Toxicology letters.

[16]  D. Mottet,et al.  CoCl2, a Chemical Inducer of Hypoxia‐Inducible Factor‐1, and Hypoxia Reduce Apoptotic Cell Death in Hepatoma Cell Line HepG2 , 2002, Annals of the New York Academy of Sciences.

[17]  B. Sarkar Metal replacement in DNA-binding zinc finger proteins and its relevance to mutagenicity and carcinogenicity through free radical generation. , 1995, Nutrition.

[18]  Catherine Méplan,et al.  Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells , 2000, Oncogene.

[19]  B. Halliwell,et al.  Nickel(II)- and cobalt(II)-dependent damage by hydrogen peroxide to the DNA bases in isolated human chromatin. , 1991, Cancer research.

[20]  S. Keith,et al.  Toxicological profile for cobalt , 2004 .

[21]  D. Lison,et al.  The interaction of cobalt metal with different carbides and other mineral particles on mouse peritoneal macrophages. , 1995, Toxicology in vitro : an international journal published in association with BIBRA.

[22]  J. Knight,et al.  Intraarticular carcinogenesis bioassays of CoCrMo and TiAlV alloys in rats. , 1995, The Journal of arthroplasty.

[23]  O. Axelson,et al.  Epidemiologic studies of occupational cancer as related to complex mixtures of trace elements in the art glass industry. , 1993, Scandinavian Journal of Work, Environment and Health.

[24]  I. Thornton,et al.  Arsenic, antimony and bismuth in soil and pasture herbage in some old metalliferous mining areas in England , 1993, Environmental geochemistry and health.

[25]  R. Lauwerys,et al.  Mutagenicity, carcinogenicity and teratogenicity of cobalt metal and cobalt compounds. , 1990, Mutation research.

[26]  J. Buchet,et al.  Increased Sister Chromatid Exchanges and Tumor-markers in Workers Exposed To Elemental Chromium-containing, Cobalt-containing and Nickel-containing Dusts , 1993 .

[27]  Benoit Nemery,et al.  In vivo genotoxicity of hard metal dust: induction of micronuclei in rat type II epithelial lung cells. , 2003, Carcinogenesis.

[28]  L. Magder,et al.  The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt , 2000, The Lancet.

[29]  M. Kirsch‐Volders,et al.  Evaluation of the in vitro direct and indirect genotoxic effects of cobalt compounds using the alkaline comet assay. Influence of interdonor and interexperimental variability. , 1998, Carcinogenesis.

[30]  M. Biagioli,et al.  Cadmium-induced apoptosis in C6 glioma cells: Mediation by caspase 9-activation , 2002, Biometals.

[31]  D. Lison,et al.  Physicochemical mechanism of the interaction between cobalt metal and carbide particles to generate toxic activated oxygen species. , 1995, Chemical research in toxicology.

[32]  Y. Kuroda,et al.  Antimutagenic action of cobaltous chloride on radiation-induced mutations in cultured Chinese hamster cells. , 1990, Mutation research.

[33]  P. Wild,et al.  Lung cancer mortality in a French cohort of hard-metal workers. , 1994, American journal of industrial medicine.

[34]  M. Kirsch‐Volders,et al.  Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt‐containing dust: A cross‐sectional study , 2000, Environmental and molecular mutagenesis.

[35]  E. Gottmann,et al.  Detection of genotoxic effects of heavy metal contaminated soils with plant bioassays. , 1998, Mutation research.

[36]  P. Wild,et al.  A mortality study of cobalt production workers: an extension of the follow-up. , 1993, American journal of industrial medicine.

[37]  A. Hartwig,et al.  Cobalt(II) inhibits the incision and the polymerization step of nucleotide excision repair in human fibroblasts. , 1997, Mutation research.

[38]  N Schaumlöffel,et al.  Heterogeneity of the DNA damage provoked by antimony and arsenic. , 1998, Mutagenesis.

[39]  H. Lantzsch,et al.  Genotoxicity of selected metal compounds in the SOS chromotest. , 1997, Mutation research.

[40]  D. Zukor,et al.  TNF-alpha secretion and macrophage mortality induced by cobalt and chromium ions in vitro-qualitative analysis of apoptosis. , 2003, Biomaterials.

[41]  S. Kevekordes,et al.  Assessment of a possible genotoxic environmental risk in sheep bred on grounds with strongly elevated contents of mercury, arsenic and antimony. , 1996, Mutation research.

[42]  G. C. Grant,et al.  Carcinogenic effects of antimony trioxide and antimony ore concentrate in rats. , 1986, Journal of toxicology and environmental health.

[43]  A. Hartwig,et al.  Differential effects of toxic metal compounds on the activities of Fpg and XPA, two zinc finger proteins involved in DNA repair. , 2000, Carcinogenesis.

[44]  Jiping Zeng,et al.  Involvement of caspase‐3 and p38 mitogen‐activated protein kinase in cobalt chloride‐induced apoptosis in PC12 cells , 2002, Journal of neuroscience research.

[45]  C. Kuo,et al.  Antimony trichloride induces DNA damage and apoptosis in mammalian cells. , 1998, Toxicology.

[46]  Masashi Kobayashi,et al.  Inhibition of proteasome activity is involved in cobalt-induced apoptosis of human alveolar macrophages. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[47]  R. Snyder,et al.  Modulation by Co(II) of UV-induced DNA repair, mutagenesis and sister-chromatid exchanges in mammalian cells. , 1991, Mutation research.

[48]  M. Thun,et al.  Mortality in a cohort of antimony smelter workers. , 1995, American journal of industrial medicine.

[49]  L. Migliore,et al.  Micronuclei assay and FISH analysis in human lymphocytes treated with six metal salts , 1999, Environmental and molecular mutagenesis.

[50]  S. Horiguchi,et al.  Genotoxicity of beryllium, gallium and antimony in short-term assays. , 1991, Mutation research.

[51]  T. Gebel Suppression of arsenic-induced chromosome mutagenicity by antimony. , 1998, Mutation research.

[52]  S. Stea,et al.  Sister chromatid exchange in patients with joint prostheses. , 2000, The Journal of arthroplasty.

[53]  H. Dunkelberg,et al.  Comparative and environmental genotoxicity of antimony and arsenic. , 1997, Anticancer research.

[54]  M. Tirmenstein,et al.  Antimony-induced oxidative stress and toxicity in cultured cardiac myocytes. , 1995, Toxicology and applied pharmacology.

[55]  J. Allen,et al.  Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects. , 2001, Carcinogenesis.

[56]  J. Haseman,et al.  Inhalation toxicity and carcinogenicity studies of cobalt sulfate. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[57]  R. Okayasu,et al.  Inhibition of DNA-double strand break repair by antimony compounds. , 2002, Toxicology.

[58]  B. Diwan,et al.  Oxidative DNA base damage in renal, hepatic, and pulmonary chromatin of rats after intraperitoneal injection of cobalt(II) acetate. , 1994, Chemical research in toxicology.

[59]  M. Kirsch‐Volders,et al.  In vitro genotoxic effects of hard metal particles assessed by alkaline single cell gel and elution assays. , 1997, Carcinogenesis.

[60]  S. Robison,et al.  Selective phagocytosis of crystalline metal sulfide particles and DNA strand breaks as a mechanism for the induction of cellular transformation. , 1982, Cancer research.

[61]  P. Wild,et al.  Lung cancer mortality in a site producing hard metals , 2000, Occupational and environmental medicine.

[62]  H Salem,et al.  Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[63]  T Gebel,et al.  Arsenic and antimony: comparative approach on mechanistic toxicology. , 1997, Chemico-biological interactions.

[64]  D. Phillips,et al.  Generation of putative intrastrand cross-links and strand breaks in DNA by transition metal ion-mediated oxygen radical attack. , 1997, Chemical research in toxicology.

[65]  E. Paleček,et al.  Effect of transition metals on binding of p53 protein to supercoiled DNA and to consensus sequence in DNA fragments , 1999, Oncogene.

[66]  G. Nordberg,et al.  Lung cancer in smelter workers--interactions of metals as indicated by tissue levels. , 1993, Scandinavian journal of work, environment & health.

[67]  A Léonard,et al.  Mutagenicity, carcinogenicity and teratogenicity of antimony compounds. , 1996, Mutation research.

[68]  S. Robison,et al.  Strand breakage and decreased molecular weight of DNA induced by specific metal compounds. , 1982, Carcinogenesis.

[69]  C. W. Jameson,et al.  Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection. , 1991, Journal of toxicology and environmental health.

[70]  S. Farah The in vivo effect of cobalt chloride on chromosomes , 1983 .

[71]  J. Mur,et al.  A cohort mortality study among cobalt and sodium workers in an electrochemical plant. , 1987, American journal of industrial medicine.

[72]  M. Bernard,et al.  Potassium antimonyl tartrate induces caspase‐ and reactive oxygen species‐dependent apoptosis in lymphoid tumoral cells , 2002, British journal of haematology.

[73]  S. Kawanishi,et al.  Active oxygen species in DNA damage induced by carcinogenic metal compounds. , 1994, Environmental health perspectives.

[74]  Dominique Lison,et al.  In vitro genotoxic effects of different combinations of cobalt and metallic carbide particles. , 2003, Mutagenesis.

[75]  M. Kirsch‐Volders,et al.  Update on the genotoxicity and carcinogenicity of cobalt compounds , 2001, Occupational and environmental medicine.

[76]  C. Verellen-Dumoulin,et al.  Increased sister chromatid exchanges and tumor markers in workers exposed to elemental chromium-, cobalt- and nickel-containing dusts. , 1993, Mutation research.