Skip to main content
SpringerLink
Log in

Partial correction of chromosome instability in Fanconi anemia by desferrioxamine

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

The action of the iron chelator desferrioxamine (DFO) on the cytogenetic pattern of cultured lymphocytes from Fanconi anemia (FA) patients was investigated. The addition of 10-4 M DFO throughout the culture time resulted in a 50% reduction of the spontaneous chromosome breakage of FA cells. In addition, the clastogenic action of diepoxybutane on FA lymphocytes was also partly counteracted by DFO. The above findings support the assumption that one of the mechanisms involved in the pathogenesis of FA might be an impaired capacity of the cells from such patients to remove active oxygen species. The relationship between intraleukocyte chelatable iron pool and free radical formation in FA subjects is discussed.

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

  • Auerbach AD, Wolman SR (1976) Susceptibility of Fanconi's anaemia fibroblasts to chromosome damage by carcinogens. Nature 261: 494–496

    Google Scholar 

  • Cerutti PA (1985) Prooxidant states and tumor promotion. Science 227:375–381

    Google Scholar 

  • Dallapiccola B, Magnani M, Novelli G, Mandelli F (1984) Increased activity of glutathione S-transferase and fast decay of reduced glutathione in Fanconi's anemia erythrocytes. Acta Haematol (Basel) 71:143–144

    Google Scholar 

  • Dallapiccola B, Porfirio B, Mokini V, Alimena G, Isacchi G, Gandini E (1985) Effects of oxidants and antioxidants on chromosomal breakage in Fanconi anemia lymphocytes. Hum Genet 69:62–65

    Google Scholar 

  • Fujiwara Y, Tatsumi M, Sasaki MS (1977) Crosslink repair in human cells and its possible defect in Fanconi's anemia cells. J Mol Biol 113:635–649

    Google Scholar 

  • Gille JJP, Wortelboer HM, Joenje H (1987) Antioxidant status in Fanconi anemia fibroblasts. Hum Genet 77:28–31

    Google Scholar 

  • Glanz A, Fraser F (1982) Spectrum of anomalies in Fanconi anemia. J Med Genet 19:412–416

    Google Scholar 

  • Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals and disease (review article). Biochem J 219:1–14

    Google Scholar 

  • Healing G, Green CJ, Simpkin S, Fuller BJ, Lunec J (1988) Desferrioxamine added to homogenates of cold-stored rabbit kidneys inhibits lipid peroxidation in vitro. Biochemistry 15:1329–1330

    Google Scholar 

  • Hershko C, Graham G, Bates GW, Rachmilewitz EA (1978) Nonspecific serum iron in thalassemia: an abnormal serum fraction of potential toxicity. Br J Haematol 40:255–263

    Google Scholar 

  • Izakovič V, Štrbáková E, Kaiserovà E, Križan P (1985) Bovine superoxide dismutase in Fanconi anaemia. Therapeutic trial in two patients. Hum Genet 70:181–182

    Google Scholar 

  • Jacobs A (1977) Low molecular weight intracellular iron transport compounds. Blood 50:433–439

    Google Scholar 

  • Joenje H, Eriksson AW, Frants RR, Arwert F, Houwen B (1978) Erythrocyte superoxide-dismutase deficiency in Fanconi's anaemia. Lancet I:204

    Google Scholar 

  • Joenje H, Arwert F, Eriksson AW, De Koning H Oostra AB (1981) Oxygen-dependence of chromosomal aberrations in Fanconi's anemia. Nature 290:142–143

    Google Scholar 

  • Kappus H (1987) Oxidative stress in chemical toxicity. Arch Toxicol 60:144–149

    Google Scholar 

  • Keberle H (1964) The biochemistry of desferrioxamine and its relation to iron metabolism. Ann NY Acad Sci 119:758–768

    Google Scholar 

  • Lederman HM, Cohen A, Lee JWW, Freedman MH, Gelfald EW (1984) Deferoxamine: a reversible S-phase inhibitor of human lymphocyte proliferation. Blood 64:748–753

    Google Scholar 

  • Nordenson I (1977) Effect of superoxide dismutase and catalase on spontaneously occurring chromosome breaks in patients with Fanconi's anemia. Hereditas 86:147–150

    Google Scholar 

  • Scarpa M, Rigo A, Momo F, Isacchi G, Novelli G, Dallapiccola B (1985) Increased rate of superoxide ion generation in Fanconi anemia erythrocytes. Biochem Biophys Res Commun 130:127–132

    Google Scholar 

  • Schroeder TM (1982) Genetically determined chromosome instability syndromes. Cytogenet Cell Genet 33:119–132

    Google Scholar 

  • Wills ED (1972) Effects of iron overload on lipid peroxide formation and oxidative demethylation by the liver endoplasmic reticulum. Biochem Pharmacol 21:239–247

    Google Scholar 

  • Wöhlers F, Schonlau F (1959) Über das Vorkommen von Ferritin im Serum. Klin Wochenschr 37:445

    Google Scholar 

  • Yoshimitsu K, Kobayashi Y, Usui T (1984) Decreased superoxide dismutase activity of erythrocytes and leukocytes in Fanconi's anemia. Acta Haematol (Basel) 72:208–210

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Public Health and Cell Biology, 2nd University of Rome, Via Orazio Raimondo, I-00173, Rome, Italy

    B. Porfirio & B. Dallapiccola

  2. Ciba-Geigy, I-35100, Padua, Italy

    G. Ambroso

  3. Department of Human Biopathology, Section of Haematology, University of Rome, “La Sapienza”, I-00161, Rome, Italy

    G. Giannella & G. Isacchi

Authors
  1. B. Porfirio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Ambroso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Giannella
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Isacchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Dallapiccola
    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

Porfirio, B., Ambroso, G., Giannella, G. et al. Partial correction of chromosome instability in Fanconi anemia by desferrioxamine. Hum Genet 83, 49–51 (1989). https://doi.org/10.1007/BF00274146

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00274146

Keywords

Search

Navigation