title: Value of in vitro models for the assessment of drug-induced haematotoxicity.
abstract: BACKGROUND
  A new antipsychotic compound induced unexpected red cell hypoplasia (reticulocytopenia, red marrow hypoplasia) in rats dosed orally for 7 days.
  
  
  METHODS
  Since an erythropoietin-mediated pathogenesis was excluded, in vitro tests on rat and human bone marrow cells were performed with measurement of formation of late erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) colony-forming units after incubation with the drug. CFU-E together with growth factors were cultured for 2 days (rat) or 7 days (human) and CFU-GM was cultured for 7 days (rat) or 10 days (human).
  
  
  RESULTS
  The drug induced inhibition of erythroid progenitors and myeloid progenitors for both species from 3 x 10(-5) mol/L, with the concentration inhibiting the growth of 50% (IC50) consistent with drug plasma levels measured in rats.
  
  
  CONCLUSIONS
  These cloning assays on rat bone-marrow cells were shown to be adequate models for determining the haematotoxicity of the agent and to be predictive of human toxicity. With only a small amount of compound required, they can be used as screening tools to detect haematotoxic potential of candidate drugs.
authors.affiliation: Drug Safety Assessment, Biologie Servier, Gidy, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Goldfain-Blanc
authors.forename: Olivier
authors.initials: O
authors.lastname: Wattrelos
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
authors.forename: Anne
authors.initials: A
authors.lastname: Beamonte
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Delongeas
authors.forename: Nancy
authors.initials: N
authors.lastname: Claude
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004921:Erythropoietin / Q000502:physiology; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000175:diagnosis*; D006801:Humans; D008954:Models, Biological; D051381:Rats; D018570:Risk Assessment; D013234:Stem Cells / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D004921:Erythropoietin