title: Comparative in vitro and ex-vivo myelotoxicity of aflatoxins B1 and M1 on haematopoietic progenitors (BFU-E, CFU-E, and CFU-GM): species-related susceptibility.
abstract: Haemato- and myelotoxicity are adverse effects caused by mycotoxins. Due to the relevance of aflatoxins to human health, the present study, employing CFU-GM-, BFU-E- and CFU-E-clonogenic assays, aimed at (i) comparing, in vitro, the sensitivity of human vs. murine haematopoietic progenitors to AFB1 and AFM1 (0.001-50microg/ml), (ii) assessing whether a single AFB1 in vivo treatment (0.3-3mg/kgb.w.) alters the ability of murine bone marrow cells to form myeloid and erythroid colonies, and (iii) comparing the in vitro with the in vitro ex-vivo data. We demonstrated (i) species-related sensitivity to AFB1, showing higher susceptibility of human myeloid and erythroid progenitors (IC(50) values: about 4 times lower in human than in murine cells), (ii) higher sensitivity of CFU-GM and BFU-E colonies, both more markedly affected, particularly by AFB1 (IC(50): 2.45+/-1.08 and 1.82+/-0.8microM for humans, and 11.08+/-2.92 and 1.81+/-0.20microM for mice, respectively), than the mature CFU-E (AFB1 IC(50): 12.58+/-5.4 and 40.27+/-6.05microM), irrespectively of animal species, (iii) regarding AFM1, a species- and lineage-related susceptibility similar to that observed for AFB1 and (iv) lack of effects after AFB1 in vivo treatment on the proliferation of haematopoietic colonies.
authors.affiliation: University of Pavia, Department of Internal Medicine and Therapeutics, Toxicology Division, Pavia, Italy. elisa.roda@unipv.it
authors.forename: E
authors.initials: E
authors.lastname: Roda
authors.forename: T
authors.initials: T
authors.lastname: Coccini
authors.forename: D
authors.initials: D
authors.lastname: Acerbi
authors.forename: A F
authors.initials: AF
authors.lastname: Castoldi
authors.forename: L
authors.initials: L
authors.lastname: Manzo
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D016607:Aflatoxin M1 / Q000633:toxicity*; D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D013045:Species Specificity
chemical_list: D009153:Mutagens; D016607:Aflatoxin M1; D016604:Aflatoxin B1