PARTIAL CHARACTERIZATION OF HUMAN LEUKEMIA U-937 CELL SUBLINES RESISTANT TO 9-NITROCAMPTOTHECIN

(H)uman leukemia U-937 cell sublines exhibiting various levels of resi stance to 9-nitrocamptothecin (9NC) were developed after exposure to p rogressively increased 9NC concentrations. Increases in 9NC resistance of the cells were accompanied by decreases in proliferation rate; app earance of morphological and functional features that correlate with g ranulocytic maturation; decreased synthesis of topoisomerase I; increa sed synthesis of topoisomerase II; and inability or decreased ability to induce tumors when xenografted in nude mice. 9NC-resistant cells, t ransferred and propagated in 9NC-free media for 6 months, continue to exhibit resistance and other features similar to cells propagated in c ontinual presence of 9NC. Finally, 9NC-resistant U-937 cells respond t o physiological and non-physiological agents of cell differentiation, indicating that alternative treatments can be successfully used to inh ibit growth of 9NC-resistant U-937 cells and tumors.