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Relevance of clonogenic assays in hematotoxicology

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Abstract

Clonogenic assays have been established in hematology for 30 years. They have been widely used in fundamental studies on hematopoiesis and they are also routinely used in clinical hematology to confirm diagnosis or to predict time to recovery in cases of bone marrow failure. Their use in toxicological studies is more recent. Adverse effects of xenobiotics can induce hematological problems and pathologies such as neutropenia, thrombocytopenia, anemia, and aplastic anemia. Three clonogenic assays are proposed for granulopoiesis, megakaryopoieisis and erythropoieisis. Hematopoietic progenitors from murine or human origin can be cultured in the presence of xenobiotics using validated protocols to complete standard animal toxicological studies. These clonogenic assays can help to predict adverse effects of drugs or toxicants. Clonogenic assays using white blood cell progenitors (CFU-GM culture) have recently been validated by ECVAM and can be used routinely. Megakaryocyte progenitor (CFU-MK) culture is under development and prevalidation in toxicological studies supported by ECVAM. Red blood cells progenitor culture (BFU-E) has been proposed but needs international validation to be recognized.

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References

  • Ascensao JL, Flynn PJ, Slungard A, Wachamn W, Zanjani ED, Jacob HS. Quinidine-induced neutropenia: a drug-dependent inhibition of granulocyte colony generation. Acta Haematol. 1984;72:349–54.

    PubMed  CAS  Google Scholar 

  • Amess J. Haematotoxicology. In: Ballantine B, Marrs T, Turner P, eds. General and applied toxicology. The MacMillan Press; 1993;1:839–67.

  • Barret AJ, Weller E, Rozengurt N, Longhurst P, Humble JG. Amidopyrine agranulocytosis: drug inhibition of granulocyte colonies in the presence of patient's serum. Br Med J. 1976;ii:850–1.

    Google Scholar 

  • Casati S, Collotta A, Gribaldo L. Human umbilical cord blood and bone marrow as a source of CD34+ CD38- cells for the in vitro CFU-MK assay. ATLA. 1999;27:120. [Abstract].

    Google Scholar 

  • Daniniak N, Worthington M, Riordan MA, Kreczko S, Goldman L. 3′-Azido-3′-deoxythimidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells. Br J Haematol. 1988;69:299–304.

    Google Scholar 

  • Deldar A, Stevens CE. Development and application of in vitro models of hematopoiesis to drug development. Toxicol Pathol. 1993;21:231–40.

    PubMed  CAS  Google Scholar 

  • Dellmann HD. Textbook of veterinary histology, 4th ed. Malvern, PA: Lea & Febinger; 1993:66.

    Google Scholar 

  • Erslev AJ. Pure red cell aplasia. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA, eds. Hematology, 4th ed. New York: Mc Graw Hill; 1990;430–8.

    Google Scholar 

  • Froquet R, Rio B, Sibiril Y, Parent-Massin D. Improvement of megakaryocyte clonogenic assay for toxicological investigations. ATLA. 1999;27:361. [Abstract].

    Google Scholar 

  • Froquet R, Sibiril Y, Parent-Massin D. Improvement of megakaryocte progenitor culture for toxicological investigations. Toxicol In Vitro. 2001 [In press].

  • Gribaldo L, Casati S, Figliuzzi L, Marafante E. In vitro myclotoxicity of environmental contaminants. Environ Toxicol Pharmacol. 1998;6:135–41.

    Article  CAS  Google Scholar 

  • Gribaldo L, Casati S, Castoldi AF, Pessina A. Comparison of in vitro drug-sensitivity of human granulocyte-macrophage progenitors from two different origins: umbilical cord blood and bone marrow. Exp Hematol. 1999;27:1593–8.

    Article  PubMed  CAS  Google Scholar 

  • Irvine AE, Morris TCM, Kelly CJ, McCraken N. Tirarcillin-induced neutropenia corroborated by in vitro CFU-C toxicity. Acta Haematol. 1983;70:364–8.

    PubMed  CAS  Google Scholar 

  • Kelton JG, Huang AT, Mold N, Logue GL, Rosse WF. The use of in vitro techniques to study drug-induced pancytopenia. N Engl J Med. 1979;301:621–4.

    Article  PubMed  CAS  Google Scholar 

  • Lautraite S, Parent-Massin D, Rio B, Hoellinger H. Comparison of toxicity induced by T-2 toxin on human and rat granulo-monocytic progenitors with an in vitro model. Hum Exp Toxicol. 1995;14:672–8.

    PubMed  CAS  Google Scholar 

  • Lind DE, Levi JA, Vincent PC. Amodiaquine-induced agranulocytosis: toxic effect of amodiaquine in bone marrow cultures in vitro. Br Med J. 1973;1:458–60.

    PubMed  CAS  Google Scholar 

  • Lord BI, Testa NG. The hemopoietic system: structure and regulation. In: Testa NG, Gale RP, eds. Hemopoiesis: long-term effects of chemotherapy and radiation. New York: Marcel Dekker; 1988:1–26.

    Google Scholar 

  • Lutton JD, Ibraham NG, Friedland M, Levere RD. The toxic effects of heavy metal on rat bone marrow in vitro erythropoiesis: protective role of hemin and zinc. Environ Res. 1984;35:97–103.

    Article  PubMed  CAS  Google Scholar 

  • Lutton JD, Mathew A, Levere RD, Abraham NG. Role of heme metabolism in AZT-induced bone marrow toxicity. Am J Hematol. 1990;35:1–5.

    PubMed  CAS  Google Scholar 

  • Parchment RE, Volpe DA, LoRusso PM, Erickson-Miller CL, Murphy MJ, Grieshaber CK. In vivo-in vitro correlation of myelotoxicity of 9-methoxypyrazoloacridine (NSC-366140, PD115934) to myeloid and erythroid hematopoietic progenitors from human, murine, and canine marrow. J Natl Cancer Inst. 1994;86:273–80.

    PubMed  CAS  Google Scholar 

  • Parchment R, Gordon M, Grieshaber CK, Sessa C, Volpe D, Ghielmini M. Predicting haematological toxicity (myelosuppression) of cytotoxic drug therapy from in vitro tests. Ann Oncol. 1998;9:357–64.

    Article  PubMed  CAS  Google Scholar 

  • Parent-Massin D, Thouvenot D. In vitro study of pesticide hematotoxicity in human and rat progenitors. J Pharmacol Toxicol Methods. 1993;30:203–7.

    Article  PubMed  CAS  Google Scholar 

  • Parent-Massin D, Sensebé L, Leglise MC, et al. Relevance of in vitro studies of drug-induced agranulocytosis. Drug Safety. 1993;9:463–9.

    Article  PubMed  CAS  Google Scholar 

  • Parent-Massin D, Fuselier R, Thouvenot D. In vitro toxicity of trichothecenes on human haematopoietic progenitors. Food Addit Contam. 1994;11:441–7.

    PubMed  CAS  Google Scholar 

  • Parent-massin D, Fournier V, Amade P, et al. Evaluation of the toxicological risk to humans of caulerpenyne using human hematopoietic progenitors, melanocytes, and keratinocytes in culture. J Toxicol Environ Health. 1996;47:47–59.

    Article  PubMed  CAS  Google Scholar 

  • Pessina A, Albella B, Bueren J, et al. Method development for a prevalidation study of the in vitro GM-CFU assay for predicting myelotoxicity. In: Balls M, van Zeller M, Halder ME, eds. Progress in the reduction, refinement and replacement of animal experimentation. Amsterdam: Elsevier Science; 2000:679–92.

    Google Scholar 

  • Rio B, Lautraite S, Parent-Massin D. In vitro toxicity of trichothecenes on human erythroblastic progenitors. Hum Exp Toxicol. 1997a;16:673–9.

    Article  PubMed  CAS  Google Scholar 

  • Rio B, Parent-Massin D. Improvement of erythroblastic progenitor culture for toxicological investigations. Toxicol Methods. 1997b;7:363–80.

    Article  CAS  Google Scholar 

  • Rio B, Parent-Massin D. Effects of diphenyl-ether herbicide oxyfluorfen on human BFU-E/CFU-E development and hemoglobin synthesis. Hum Exp Toxicol. 1997c;16:11–22.

    Google Scholar 

  • Van den Heuvel R, Leppens H, Bertels N, Schoeters G. Comparison of haematotoxicity induced by lead and the benzene metabolites catechol and hydroquinone on human and murine haematopoietic progenitor cells using in vitro assays. Cell Biol Toxicol. 1999a;15:101–10.

    Article  PubMed  CAS  Google Scholar 

  • Van den Heuvel R, Leppens H, Nuyten J-M, Schoeters G. Haematopoietic lineage sensitivity and individual susceptibility to PCB126: relation to glutathione-S-transferase. Toxicol In Vitro. 1999b;13:605–9.

    Article  CAS  PubMed  Google Scholar 

  • Yamaguchi F, Furuhama K, Miyamoto M, Sagara-Ishijama N, Takayama S. Application of hematopoietic progenitors assays for the estimation of hematotoxicity in rats. J Pharmacol Toxicol Methods. 1994;31:71–7.

    Article  PubMed  CAS  Google Scholar 

  • Young NS. Drugs and chemicals. In: Young NS, ed. Aplastic anemia, acquired and inherited. Philadelphia, PA: Saunders; 1994:100.

    Google Scholar 

  • Yunis AA, Miller AM, Salem Z, Arimura GK. Chloramphenicol toxicity: pathogenetic mechanisms and the role of the p-NO2 in aplastic anemia. Clin Toxicol. 1980;17:359–73.

    Article  PubMed  CAS  Google Scholar 

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  1. Laboratoire de Microbiologie et Sécurité Alimentaire, Ecole Supérieure de Microbiologie et Sécurité Alimentaire de Brest, ESMISAB/ISAMOR, Plouzané, France

    D. Parent-Massin

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Parent-Massin, D. Relevance of clonogenic assays in hematotoxicology. Cell Biol Toxicol 17, 87–94 (2001). https://doi.org/10.1023/A:1010906104558

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