Clastogenic Factors as Biomarkers of Oxidative Stress

Their Usefulness for Evaluation of the Efficacy of Antioxidant Treatments
  • Ingrid Emerit
Part of the NATO ASI Series book series (NSSA, volume 296)


Clastogenic factors (CF) have been recognized since the early seventieth as an indirect effect of ionizing radiation (Goh and Sumner, 1968; Hollowell and Littlefield, 1968). Because of their persistence in the blood of irradiated persons many years after exposure, they have been considered as risk factors for late effects of radiation, such as cancer and leukemia (Faguet, 1984). Previous work of our laboratory has shown that CF are not specific for irradiated subjects, but found in a variety of other pathological conditions, where they are biomarkers of oxidative stress. Their formation and their clastogenic action are related to increased superoxide production, since both are regularly inhibited by superoxide dismutase (SOD) (Emerit, 1994). They are not single factors, as thought by the first observers, but mixtures of chromosome-damaging pro-oxidant substances. Nevertheless the term “clastogenic factor” has been conserved.


Familial Mediterranean Fever Superoxide Production Fanconi Anemia Ginkgo Biloba Extract PUVA Therapy 
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  1. Alaoui-Youssefi, A., Aroutiounian, R., Emerit I., 1994, Chromosome damage in PUVA-treated human lymphocytes is related to active oxygen species and clastogenic factors, Mutat. Res. 309: 185–191.Google Scholar
  2. Auclair, C., Gouyette, A., Levy, A., Emerit, I., 1990, Clastogenic inosine nucleotides as components of the chromosome breakage factor in scleroderma patients, Arch. Biochem. Biophys. 278: 238–244.CrossRefGoogle Scholar
  3. Camus, J.P., Emerit, I., Michelson, A.M., Prier, A., Koeger, A.C., Merlet, C., 1980, Superoxide dismutase et polyarthrite rhumatoide, Revue du Rhumatism 47: 489–492.Google Scholar
  4. Degan, P., Bonassi, S., De Caterina, M., Korkina, L., Pinto, L., Scopascasa, F., Zatterale, A., Calzone, R., Pagano, G., 1995, In vivo accumulation of 8-hydroxy-2’-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi’s anemia families; Carcinogenesis 16: 735–742.Google Scholar
  5. Edeas, M.A., Emerit, I., Khalfoun, Y., Lazizi, Y., Cernjayski, L., Levy, A., Lindenbaum, A. 1997, Clastogenic factors in plasma of HIV-infected patients activate HIV-1 replication in vitro. Inhibition by superoxide dismutase, 23: in pressGoogle Scholar
  6. Emerit, I., 1990 a, Superoxide production by clastogenic factors, in Free Radicals, Lipoproteins and Membrane Lipids (A. Crastes de Paulet, L. Douste-Blazy and R. Paoletti, eds.), pp. 99–104, Plenum Press, New York.Google Scholar
  7. Emerit, I., 1990 b, Clastogenic factors: Detection and assay, in: Methods in Enzymology, (L. Packer and A.N. Glazer, eds;), pp. 555–564, Academic Press, New York.Google Scholar
  8. Emerit, I., 1991, Membrane-mediated chromosome damage anf formation of clastogenic factors, in:Membrane lipid oxidation (C. Vigot-Pelfrey, ed.), pp. 33–43, CRC Press, Boca Raton.Google Scholar
  9. Emerit, I., 1994, Reactive oxygen species, chromosome mutation and cancer: possible role of clastogenic factors in carcinogenesis, Free Radic. Biol. Med. 16: 99–109.Google Scholar
  10. Emerit, I. and Michelson, A.M. 1981a, Mechanisms of photosensitivity in systemic lupus erythematosus patients, Proc. Natl. Acad. Sci., USA, 8: 2537–2540.CrossRefGoogle Scholar
  11. Emerit, I. and Michelson, A.M. 198 lb, Chromosomal breakage in Crohn’s disease, in: Recent Advances in Crohn’s Disease (Pena, A.S., Weterman, I.T., Booth, CC., Strober, W., eds.), pp. 225–229, Martinus Nijhoff Publishers, The Hague.Google Scholar
  12. Emerit, I. and Cerutti, P. 1981, Clastogenic activity from Bloom’s syndrome fibroblast cultures, Proc. Natl. Acad. Sci. USA 78: 1868–1872.CrossRefGoogle Scholar
  13. Emerit, I. and Cerruti, P., 1982, Tumor promoter phorbol-myristate acetate induces a clastogenic factor in human lymphocytes, Proc. Natl. Acad. Sci. USA, 79: 7509–7513.CrossRefGoogle Scholar
  14. Emerit, I. and Lahoud-Maghani, 1989, Mutagenic effects of TPA-induced clastogenic factor in Chinese hamster cells, Mutat. Res. 214: 97–104.Google Scholar
  15. Emerit, I., Levy, A., Michelson, A.M. 1981, Effect of superoxide dismutase on the chromosomal instability of New Zealand black mice, Cytogenet. Cell Genet. 30: 65–69.CrossRefGoogle Scholar
  16. Emerit, I., Fabiani, J.N., Ponzio, O., Murday, A., Lunel, F., Carpentier, A. 1988, Clastogenic factor in ischemia-reperfusion injury during open-heart surgery: Protective effect of Allopurinol, Ann. Thorac. Surg. 46: 619–624.CrossRefGoogle Scholar
  17. Emerit, I., Levy, A. and Camus, J.P. 1989, Monocyte-derived clastogenic factor in rheumatoid arthritis, Free Radic. Biol. Med. 6: 245–250.Google Scholar
  18. Emerit, I., Khan, S.H. and Esterbauer, H. 1991, Hydroxynonenal, a component of clastogenic factors? Free Radic. Biol. Med. 10: 371–377.Google Scholar
  19. Emerit, I., Aroutiounian, R., Sarkisian, T., Torossian, E. and Panossian, A.G. 1993, Oxyradical-related chromosome damage in patients with Familial Mediterranean Fever, Free Radic. Biol. Med. 15: 265–271.Google Scholar
  20. Emerit, I., Levy, A., Cemjayski, L., Aroutiounian, R., Panassian, A., Pogossian, A., Mejlumian, H., Sarkisian, T., Gulkandanian, M., Quastel, M., Goldsmith, J., Riklis, E., Kordysh, R., Poliak, S. Merklin, 1994, Transferable clastogenic activity in plasma from persons exposed as salvage personnel of the Chernobyl reactor. J. Cancer Res. Clin. Oncol. 120: 558–561.CrossRefGoogle Scholar
  21. Emerit, I., Levy, A., Pagano, G., Pinto, L., Calzone, R., Zatterale, A. 1995a, Transferable clastogenic activity in plasma from patients with Fanconi anemia, Hum. Genet. 96: 14–20.Google Scholar
  22. Emerit, I., Fabiani, J.N., Levy, A., Ponzio, O., Conti, M., Brasme, B., Bienvenu, P., Hatmi, M. 1995b, Plasma from patients exposed to ischemia reperfusion contains clastogenic factors and stimulates the chemiluminescence response of normal leukocytes, Free Radic. Biol. Med. 19: 405–415.Google Scholar
  23. Emerit, I., Oganesian, N., Sarkisian, T., Arutiounian, R., Pogossian, A., Asrian, K., Levy, A., Cernjayski, L. 1995c, Clastogenic factors in the plasma of Chernobyl accident recovery workers: anticlastogenic effect of Ginkgo biloba extract, Radiation Res. 144: 198–205.CrossRefGoogle Scholar
  24. Emerit, I., Garban, F., Vassy, J., Levy, A., Filipe, P., Freitas, J. 1996, Superoxide-mediated clastogenesis and anticlastogenic effects of exogenous superoxide dismutase, Proc. Natl. Acad. Sci. USA 93: 12799–12804.CrossRefGoogle Scholar
  25. Emerit, I., Quastel, M., Goldsmith, J., Merkin, L., Levy, A., Cernjayski, L., Alaoui-Youssefi, A., Pogossian, A., Riklis, E. 1997a, Clastogenic factors in the plasma of children exposed at Chernobyl, Mutat. Res. 373: 47–54.Google Scholar
  26. Emerit, I., Filipe, P., Meunier, P., Auclair, C., Freitas, J., Deroussent, A., Gouyette, A., Fernandez, A. 19976, Clastogenic factors in plasma of scleroderma patients: as biomarker of oxidative stress, Dermatology, 194: 140–146.Google Scholar
  27. Emerit, I., Oganesian, N., Aroutiounian, R., Pogossian, A., Sarkisian, T., Cernjayski, L., Levy, A., Feingold, J. 1997d, Oxidative stress-related clastogenic factors in plasma from Chernobyl liquidators: protective effects of antioxidant plant phenols, vitamins and oligoelements, Mutat. Res. in press.Google Scholar
  28. Faguet, G.G., Reichard, S.M., Welter, D.A., 1984, Radiation-induced clastogenic plasma factors, Cancer Genet. Cytogenet. 12: 73–83.CrossRefGoogle Scholar
  29. Filipe, P., Emerit, I., Alaoui-Youssefi, A., Levy, A., Cemjayski, L., Freitas, J., Cime de Castro, J.L. 1997, Oxyradicalmediated clastogenic plasma factors in psoriasis. Increase in clastogenic activity after PUVA, submitted.Google Scholar
  30. Fuchs, J., Emerit, I., 1995, Clastogenic factors in plasma of HIV-infected patients, Free Radic. Biol. Med. 19: 843–848.Google Scholar
  31. Gabrielian, E., Grigorian, S., Davidian, D., Mchitarian, G., Panossian, A., 1990, Leukotrienes B4 and C4 in blood plasma of patients with Familial Mediterranean Fever, Bull. Exp. Biol. Med. 110: 296–297.Google Scholar
  32. Gille, J.J.P., Wortelboer, H.M., Joenje, H., 1989, Antioxidant status of Fanconi fibroblasts, in: Hyperoxia-induced oxidative stress in mammalian cell cultures, ( J.J.P. Gille ed.), pp. 79–88, Free University Press, Amsterdam.Google Scholar
  33. Goh, K.O., Sumner, K., 1968, Breaks in normal human chromosomes are they induced by a transferable substance in the plasma of irradiated persons exposed to total-body irradiation?, Radiation Res. 6: 51–60.Google Scholar
  34. Harth, M., Keown, P.A., Orange, J.F., 1983, Monocyte-dependent excited oxygen radical generation in rheumatoid arthritis, J. Rheumatol. 10: 701–707.Google Scholar
  35. Hallahan D.E., Spriggs, D.R., Beckett, M.A., Kufe, D., Weichselbaum, R.R., 1989, Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation, Proc. Natl. Acad. Sci. USA 886: 10104–10107.CrossRefGoogle Scholar
  36. Hollowell, H.G., Littlefield, L.G., 1968, Chromosome damage induced by plasma from irradiated patients. An indirect effect of X-ray, Proc. Soc. Exp. Biol. Med. 129: 240–244.Google Scholar
  37. Iwamoto, K.S., McBride, W.H., 1994, Production of 13-hydroxy-octadecadienoic acid and tumor necrosis factor alpha by murine peritoneal macrophages in response to irradiation. Radiation Res. 139: 103–108.CrossRefGoogle Scholar
  38. Joenje, H., Arwert, F., Erikson, A.W., DeKoning, H., Ostra, A.B., 1981, Oxygen dependence of chromosomal aberrations in Fanconi’s anemia, Nature, 290: 142–143.CrossRefGoogle Scholar
  39. Kalebic, T., Kinter, A., Poli, G., Anderson, M.E., Meister, A., Fauci, A.S., 1991, Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine, Proc. Natl. Acad. Sci. USA 88: 986–990.CrossRefGoogle Scholar
  40. Kellof, G.J., Boone, C.W., Malone, W.F., Steele, V.E., 1992, Chemoprevention clinical trials, Mutat. Res. 267: 291–295.Google Scholar
  41. Khan, S.H., Emerit, I., Feingold, J., 1990, Superoxide and hydrogen peroxide production by macrophages of NZB mice, Free Radic. Biol. Med. 8: 339–345.Google Scholar
  42. Korkina, L.G., Samochatova, E.V., Mashan, A.A., Suslova, T.B., Cheremissina, Z.P., Afanas“ev, I.B., 1992, J. Leukocyte Biol. 52: 357–363.Google Scholar
  43. Krivenko, S., Dryk, S., Komarovskaya, M., Karkanitsa, L., 1992, Ionizing radiation increases TNF/cachectin production in human peripheral mononuclear cells in vitro, Int. J. Hematol. 55: 127–130.Google Scholar
  44. Kuhns, D.B., Wright, D.G., Nath, J., Kaplan, S.S., Basford, R.E. ATP induces transient elevations of Cat. in human neutrophils and primes cells for enhanced O2 production, Lab. Invest. 58: 448–53.Google Scholar
  45. Matzner, Y., Brzezinki, R., 1984, C5a inhibitor deficiency in peritoneal fluid from patients with Familial Mediterranean Fever, New Engl. J. Med. 311: 287–290.Google Scholar
  46. McCord, J.M., 1985, Oxygen-derived free radicals in postischemic tissue injury, N. Engl. J. Med. 312: 159–162.CrossRefGoogle Scholar
  47. Miesel, R., Zuber, M. 1993, Elevated levels of xanthine oxidase in serum of patients with inflammatory and autoimmune rheumatic diseases, Inflammation 17: 551–561.CrossRefGoogle Scholar
  48. Neriishi, K., Possible involvement of a free radical mechanism in late effects of A-bomb radiation. Proc. 5th, Int. Congr. on Oxygen Radicals: Active Oxygen, Lipid Peroxides and Antioxidants, Kyoto, 1991, Abstr.Google Scholar
  49. Pant, G.S., Kamada, N., 1977, Chromosome aberrations in normal human leukocytes induced by the plasma of exposed inividuals. Hiroshima J. Med. Sci. 26: 149–154.Google Scholar
  50. Rogers, D.B;, Shohat, M., Petersen, G.M., Bickal, J., 1989, Familial Mediterranean Fever in Armenians: Autosomal recessive inheritance with high gene frequency. Amer. J. Med. Genet. 34: 168–172.Google Scholar
  51. Roselli, F, Sanceau, J., Gluckman, E., Wietzerbin, J., Moustacchi, E., 1994, Abnormal lymphokine production: A novel feature of the genetic disease Fanconi anemia. II. In vitro and in vivo spontaneous overproduction of tumor necrosis factor alpha. Blood, 83: 1216–1225.Google Scholar
  52. Saito, H., Hammond, A.T., Moses, R.E., 1993, Hypersensitivity to oxygen is a uniform and secondary defect in Fanconi anemia cells. Mutat. Res. 294: 255–262.CrossRefGoogle Scholar
  53. Shaham, M., Becker, Y., 1986, The ataxia telangiectasia clastogenic factor is a low molecular weight peptide. Hum. Genet. 75: 197–208.Google Scholar
  54. Wavra, E., Zollner, H., Schaur, R.J., Tillian, H.M., Schauenstein, E., 1986, The inhibitory effect of 4-hydroxynonenal on DNA polymerases alpha and beta from rat liver and rapidly dividing Yoshida ascites hepatoma. Cell Biochem. Function 4: 31–36.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Ingrid Emerit
    • 1
  1. 1.Free Radical Research Group Institut biomédical des CordeliersUniversity Paris VIFrance

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