Partial characterization of human leukemia U-937 cell sublines resistant to 9-nitrocamptothecin.
Human leukemia U-937 cell sublines exhibiting various levels of resistance to 9-nitrocamptothecin (9NC) were developed after exposure to progressively increased 9NC concentrations. Increases in 9NC resistance of the cells were accompanied by decreases in proliferation rate; appearance of morphological and functional features that correlate with granulocytic maturation; decreased synthesis of topoisomerase I; increased synthesis of topoisomerase II; and inability or decreased ability to induce tumors when xenografted in nude mice. 9NC-resistant cells, transferred and propagated in 9NC-free media for 6 months, continue to exhibit resistance and other features similar to cells propagated in continual presence of 9NC. Finally, 9NC-resistant U-937 cells respond to physiological and non-physiological agents of cell differentiation, indicating that alternative treatments can be successfully used to inhibit growth of 9NC-resistant U-937 cells and tumors.
Pantazis
P
P
Stehlin Foundation for Cancer Research, St. Joseph Hospital, Houston, Texas 77003.
Mendoza
J T
JT
DeJesus
A
A
Rubin
E
E
Kufe
D
D
Giovanella
B C
BC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000032:analysis / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004351:Drug Resistance; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004264:DNA Topoisomerases, Type I; C079905:rubitecan; D013755:Tetradecanoylphorbol Acetate; D002166:Camptothecin