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Titolo:
Inhibition of CFU-E/BFU-E by 3 '-azido-3 '-deoxythymidine, chlorpropamide,and protoporphirin IX zinc (II): A comparison between direct exposure of progenitor cells and long-term exposure of bone marrow cultures
Autore:
Gribaldo, L; Malerba, I; Collotta, A; Casati, S; Pessina, A;
Indirizzi:
Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect,European Ctr Validat Alternat Methods, I-21020 Ispra, Italy Commiss European Communities Ispra Italy I-21020 s, I-21020 Ispra, Italy Univ Milan, Inst Microbiol, Milan, Italy Univ Milan Milan ItalyUniv Milan, Inst Microbiol, Milan, Italy
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 58, anno: 2000,
pagine: 96 - 101
SICI:
1096-6080(200011)58:1<96:IOCB3'>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VITRO; DRUG DEVELOPMENT; TOXICITY; INVITRO; HEMATOPOIESIS; COLONIES;
Keywords:
CFU-E; BFU-E; CFU-GM; human umbilical cord blood; long-term murine bone marrow cultures;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Gribaldo, L Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect,European Ctr Validat Alternat Methods, I-21020 Ispra, Italy Commiss European Communities Ispra Italy I-21020 spra, Italy
Citazione:
L. Gribaldo et al., "Inhibition of CFU-E/BFU-E by 3 '-azido-3 '-deoxythymidine, chlorpropamide,and protoporphirin IX zinc (II): A comparison between direct exposure of progenitor cells and long-term exposure of bone marrow cultures", TOXICOL SCI, 58(1), 2000, pp. 96-101

Abstract

Erythropoiesis occurs in two stages: proliferation amplifies cell number, and differentiation stimulates the acquisition of the functional propertiesof red blood cells. The erythroid colony-forming unit (CFU-E) amplifies the differentiation process in response to erythropoietic stress in vitro, whereas the burst-forming unit (BFU-E), which is not particularly sensitive to erythropoietin stimulation, gives rise to the CFU-E and, when stimulated,produces morphologically-identifiable erythroid colonies. The aim of this work was to evaluate the toxic effects of the antiviral agent, 3'-azido-3'-deoxythymidine (AZT), the antidiabetic drug, chlorpropamide (CLP), and the heme-analogous compound, protophorphirin IX zinc (II) (ZnPP), on the proliferation of erythroblastic progenitors by using human umbilical-cord blood cells and murine progenitors from long-term bone marrow cultures. All these agents may interfere with the hemopoietic process, causing myelotoxicity asan adverse effect via different mechanisms. Our results showed selective toxicity of the three drugs on the erythroid progenitors (IC50: AZT 0.35 +/-0.13 muM, ZnPP 23.34 +/- 1.16 muM, CLP 1.07 +/- 0.27 mM), with respect to the myeloid progenitors (IC50: AZT 0.8 muM, ZnPP 103.9 +/- 3.9 muM and CLP > 2800 muM). The IC50 values were well correlated with peak plasma levels reached in vivo by the drugs. There was a marked similarity between the drugsensitivities of the human and murine progenitors but differences in toxicity exerted by the drugs on the basis of the time of exposure. Drug treatment of long-term cultures, followed by the clonogenic assay of progenitors collected from them in the absence of the drugs, generally resulted in a lower hematotoxicity.

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Documento generato il 06/07/20 alle ore 03:43:56