The A.H.E.A.D. method: a quantitative automated measurement of the hematotoxicity of anticancer drugs.
Among the limiting side-effects of anticancer drugs, hematological toxicity is the most frequent. Hematological analysis focuses on nucleated blood cells from mouse peripheral blood or hematopoietic organs (bone marrow, spleen, thymus). We have developed an automated method called A.H.E.A.D. (Automated Hematotoxicological Evaluation of Anticancer Drugs) allowing us routinely to screen chemical products for hematotoxicity, simultaneously with in vivo and in vitro antitumoral assays. Data are collected after a simple dilution of biological samples without any additional isolation, enrichment or purification process. The measurements are performed through an electronic Coulter counter and a slightly modified pulse-height model C1000 analyzer connected on-line to a computer. In addition to nucleated cell counts, this method allows us to get information about cell volume distribution within a given population of leukocytes. In bone marrow, a single assay provides simultaneous information on the relative contents of red, lymphoid, polymorphonuclear and blast cells. We present results obtained with this method during the hematological toxicity studies of some standard anticancer drugs. Besides drug induced alterations, the A.H.E.A.D. method allows monitoring of the recovery of hematological tissues characterization of growing populations of precursors renewing the hematopoietic organs.
Saint-Dizier
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Institut de Recherches Servier, Suresnes, France.
Sancier
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Cudennec
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D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001322:Autoanalysis / Q000379:methods; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002330:Carmustine / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005472:Fluorouracil / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D014747:Vinblastine / Q000633:toxicity
D000970:Antineoplastic Agents; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D002330:Carmustine