SENSITIVITY OF CAMPTOTHECIN-RESISTANT HUMAN LEUKEMIA-CELLS AND TUMORSTO ANTICANCER DRUGS WITH DIVERSE MECHANISMS OF ACTION

Human leukemia U-937 cell clones resistant to 9-nitrocamptothecin (9NC ) appear after exposure to increase 9NC-concentrations. Drug resistanc e is irreversible, regardless of whether the 9NC-resistant (U-937/CR15 0) cells grow in media with or without 9NC. U-937/CR150 cells are more sensitive than wild type U-937 (U-937/wt) cells to topoisomerase II-d irected drugs, amsacrine, daunorubicin, and etoposide. The mitotic inh ibitor, vincristine, induces hyperdiploidy in U-937/wt, but not in U-9 37/CR150 cells, whereas the antimetabolites, cytarabine and methotrexa te, and the nitrosourea, carmustine, elicit similar responses in both U-937/wt and U-937/CR150 cells. U-937/CR150-generated tumors in nude m ice are sensitive to etoposide. The clinical implications of increased sensitivity of SNC-resistant tumors to some anticancer drugs are disc ussed.