DEVELOPMENT OF RESISTANCE TO 9-NITRO-CAMPTOTHECIN BY HUMAN LEUKEMIA U-937 CELLS IN-VITRO CORRELATES WITH ALTERED SENSITIVITIES TO SEVERAL ANTICANCER DRUGS

We have recently reported that exposure of human leukemia U-937 cells to progressively increasing concentrations of 9-nitro-camptothecin (9N C) resulted in cell sublines exhibiting various levels of resistance t o 9NC. Here, we report responses of wild-type (U-937/wt) and 9NC-resis tant (U-937/CR) cells to various anticancer cs used extensively in can cer chemotherapy. U-937/CR cells were more sensitive than U-937/wt cel ls to several commonly used drugs of diverse origin including the topo isomerase II-directed drugs amsacrine, etoposide and daunorubicin; the vinca alkaloid vincristine; and the antimetabolite methotrexate. No r esponses were induced by carmustine in either cell type, whereas simil ar responses were induced by cytarabine. The sensitivity to the drugs was investigated by monitoring cell proliferation, by determining cell cycle perturbations assessed by flow cytometry analysis of DNA conten t and by microscopy of stained cells. The results in this report indic ate that development of 9NC resistance by the U-937 cells is accompani ed by increased sensitivities to other anticancer drugs in vitro and v ery likely in vivo.