Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents

Toxicology in Vitro : an International Journal Published in Association with BIBRA
D A Volpe, M K Warren

Abstract

A battery of clonal assays for myeloid progenitor cells (HPP-CFC, CFU-gemm, CFU-gm, CFU-g) was utilized to evaluate the myelotoxicity of a series of alkylating agents representing the spectrum of clinical times to nadir. Bone marrow aspirates from normal volunteers were incubated with mechlorethamine, busulfan, melphalan, carmustine or lomustine for 1 h and then cultured in methylcellulose with 30% serum and cytokines. There was a concentration-dependent inhibition of colony formation and often a differential toxicity to the myeloid progenitors with the alkylators tested. On a molar basis, mechlorethamine and melphalan were the most toxic of the alkylator drugs to the myeloid precursors. The most sensitive progenitor was CFU-gemm with the lowest inhibitory concentration IC(70) concentrations for mechlorethamine, melphalan, carmustine and lomustine. Generally, there was great similarity for drug effects between CFU-g and CFU-gm with overlapping inhibition curves. HPP-CFC proved to be the least sensitive of the progenitors to the toxic actions of the drugs. While there was no correlation between the time to clinical neutropenic nadir and the most sensitive progenitor in the clonal assays, the CFU-gm assay remains a suitable metho...Continue Reading

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Citations

Sep 4, 2009·Cancer Chemotherapy and Pharmacology·Holger Peter BehrsingRalph E Parchment
Jan 13, 2015·Chemotherapy Research and Practice·Ebenezer Tunde OlayinkaOluwatobi Adewumi Adeyemo
Aug 23, 2008·Journal of Cancer Research and Clinical Oncology·M Schmidt-HieberI W Blau
Feb 14, 2015·Drug and Chemical Toxicology·Navneet Kumar YadavR K Singh
Mar 25, 2010·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·El-Sayed M El-SayedAhmed S Saad
May 31, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·El-Sayed M El-SayedAhmed S Saad
Apr 25, 2007·Pediatric Hematology and Oncology·Nesrin Zeynep ErtanKadriye Akgun-Dar
Aug 17, 2017·Anais Da Academia Brasileira De Ciências·Nícolas C C PintoRodrigo L Fabri
Nov 4, 2009·Toxicology·D Parent-MassinY Sibiril

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