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Abstract
The rapid rate of blood cell renewal makes the hematopoietic system a susceptible target for xenobiotic toxicity, and xenobiotics could interfere with cell proliferation and differentiation. Hematotoxic molecules can affect one or more hematopoietic lineages, leading to blood disorders (neutropenia, agranulocytosis, thrombopenia, anemia, and pancytopenia). Erythropoiesis is the part of hematopoiesis responsible for red blood cell production by proliferation and differentiation of specific erythroblastic progenitors, the BFU-E/ CFU-E (Burst and Colony-Forming Unit-Erythroid). Some drugs and chemicals (antituberculosis drugs, chloramphenicol, penicillamines, ethanol, and lead) are able to cause dysfunction in heme biosynthesis and are responsible for hematological diseases such as porphyrias. The aim of this work was to obtain a useful tool to predict the toxic effect of xenobiotics in the proliferation or erythroblastic progenitors and on their differentiation. Optimal growth conditions for erythroblastic progenitor culture were investigated to define a cell culture model for toxicological investigations that can perform a morphological study of cells as well as an evaluation of cell abilities to synthetize porphyrins and hemoglobin in vitro. Biochemical dosages by spectrophotometry and chromatography have been adapted to this clonogenic assay on cells obtained after BFU-E/ CFU-E proliferation and differentiation. The effects of two pesticides (lindane \[organochlorine insecticide] and oxyfluorfen \[diphenyl-ether herbicide]) and two mycotoxins (T-2 toxin \[trichothecene mycotoxin] and fumonisin B1) were studied on BFU-E/ CFU-E development to validate this extension of clonogenic assay to toxicology.