title: In vitro myelotoxicity of propanil and 3,4-dichloroaniline on murine and human CFU-E/BFU-E progenitors.
abstract: Because of the wide use of pesticides for domestic and industrial purposes, the evaluation of their potential effects is of major concern for public health. The myelotoxicity of the herbicide propanil (3,4-dichloroproprioanilide) and its metabolite 3,4-dichloroaniline (DCA) is well documented in mice, but evidence that pesticides may severely compromise hematopoiesis in humans is lacking. In this study, an interspecies comparison of in vitro toxicity of these two compounds on murine and human burst- and colony-forming unit-erythrocyte (BFU-E, CFU-E) and colony-forming unit-granulocyte/macrophage (CFU-GM) progenitors, has been carried out. Murine bone marrow progenitors and human cord blood cells were exposed to propanil or DCA in doses ranging from 10 micro M to 1000 micro M, and the toxic effect was detected by a clonogenic assay with continuous exposure to the compounds. The results on murine cells indicate that the erythrocytic lineage is the most sensitive target for propanil and DCA. On the other hand, human progenitors seem to be less sensitive to the toxic effects of both compounds than murine progenitors at the same concentrations (IC(50) values are 305.2 +/- 22.6 micro M [total erythroid colonies] and >500 micro M [CFU-GM] for propanil). Propanil was significantly more toxic to human erythroid progenitors than to human CFU-GM progenitors, as was found for the murine cells, emphasizing the role of the heme pathway as the target for propanil. These data confirm the evidence that the compounds investigated interfere with erythroid colony formation at different stages of the differentiation pathway and have different effects according to the dose.
authors.affiliation: Laboratory of Hematotoxicology, ECVAM, Institute for Health and Consumer Protection, J.R.C., Ispra 21020, Italy. ilaria.malerba@jrc.it
authors.forename: I
authors.initials: I
authors.lastname: Malerba
authors.forename: A F
authors.initials: AF
authors.lastname: Castoldi
authors.forename: D
authors.initials: D
authors.lastname: Parent-Massin
authors.forename: L
authors.initials: L
authors.lastname: Gribaldo
mesh_terms: D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D001855:Bone Marrow Diseases / Q000139:chemically induced*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D011411:Propanil / Q000633:toxicity*
chemical_list: D000814:Aniline Compounds; D006540:Herbicides; C014464:3,4-dichloroaniline; D011411:Propanil