title: In vitro tests for haematotoxicity: prediction of drug-induced myelosuppression by the CFU-GM assay.
abstract: In a prevalidation study, a standard operating procedure (SOP) for human and mouse in vitro tests was developed, for evaluating the potential haematotoxicity of xenobiotics in terms of their direct, adverse effects on the myeloid colony-forming unit (CFU-GM). Based on the adjustment of the mouse-derived maximum tolerated dose (MTD), a prediction model was set up to calculate the human MTD, and an international blind trial was designed to apply this model to the clinical neutropenia of 23 drugs including 17 antineoplastics. The model correctly predicted the human MTD for 20 drugs out of the 23 (87%). This high percentage of predictivity, and the reproducibility of the SOP testing, confirmed the scientific validation of this model, and suggest promising applications for developing and validating other in vitro methods for use in haematotoxicology.
authors.affiliation: Institute of Microbiology, University of Milan, via Pascal 36, 20133 Milan, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Pessina
authors.forename: Beatriz
authors.initials: B
authors.lastname: Albella
authors.forename: Maria
authors.initials: M
authors.lastname: Bayo
authors.forename: Juan
authors.initials: J
authors.lastname: Bueren
authors.forename: Paul
authors.initials: P
authors.lastname: Brantom
authors.forename: Silvia
authors.initials: S
authors.lastname: Casati
authors.forename: Cristina
authors.initials: C
authors.lastname: Croera
authors.forename: Ralph
authors.initials: R
authors.lastname: Parchment
authors.forename: Dominique
authors.initials: D
authors.lastname: Parent-Massin
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
authors.forename: Yann
authors.initials: Y
authors.lastname: Sibiri
authors.forename: Rosette
authors.initials: R
authors.lastname: Van Den Heuvel
authors.forename: Laura
authors.initials: L
authors.lastname: Gribaldo
mesh_terms: D000208:Acute Disease; D000826:Animal Testing Alternatives; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D003114:Colony-Forming Units Assay; D006801:Humans; D020128:Inhibitory Concentration 50; D007753:Laboratories / Q000592:standards; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009503:Neutropenia / Q000139:chemically induced* / Q000473:pathology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D015262:Xenobiotics / Q000145:classification / Q000633:toxicity*
chemical_list: D015262:Xenobiotics