Inhibition by chemotherapeutic agents of human bone marrow progenitor cells and clonogenic cells of a lymphoblastic cell line

Abstract

Using methylcellulose based semi-solid medium enriched with complete alpha medium and undialysed fetal calf serum, we compared the cytotoxic effects between the clonogenic cell (CFU) of a lymphoblastic leukemia cell line (MOLT-4) and normal bone marrow granulocytic progenitor cells (CFU-C) of methotrexate (MTX), vincristine (VCR), hydrocortisone (HC) and daunorubicin (DNR), as well as the reversibility by leukovorin (LV) of MTX cytotoxicity. The neoplastic cells were more markedly inhibited by MTX, VCR and HC following either brief or continuous exposure of the cell to the drugs. Inhibition by DNR was identical for both cell types. In order to reverse the inhibitory effects of MTX in MOLT-4 CFU, LV concentrations needed were at least one log order higher than MTX concentrations. At higher concentrations of MTX, LV reversal was less effective. Only one of four different human bone marrows studied were significantly inhibited by MTX under the experimental conditions. It is suggested that the high concentrations of nucleosides and deoxynucleosides present in the medium aborted the MTX cytotoxicity on CFU-C of normal human marrow but not on MOLT-4 CFU, while the differential inhibition observed with VCR and HC was due to greater sensitivity of the leukemic cells.