In vitro tests for haematotoxicity: prediction of drug-induced myelosuppression by the CFU-GM assay.
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.
Pessina
Augusto
A
Institute of Microbiology, University of Milan, via Pascal 36, 20133 Milan, Italy.
Albella
Beatriz
B
Bayo
Maria
M
Bueren
Juan
J
Brantom
Paul
P
Casati
Silvia
S
Croera
Cristina
C
Parchment
Ralph
R
Parent-Massin
Dominique
D
Schoeters
Greet
G
Sibiri
Yann
Y
Van Den Heuvel
Rosette
R
Gribaldo
Laura
L
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*
D015262:Xenobiotics