Inducibility of terminal differentiation in daunomycin- and cytosine arabinoside-resistant mouse myeloid leukemia M1 cells.
Studies were made on whether differentiation and proliferation of antitumor drug-resistant leukemia cells could be controlled by specific inducers of terminal differentiation. Leukemia subclones resistant to daunomycin and/or cytosine arabinoside were isolated from differentiation-inducible mouse myeloid leukemia M1-B24 cells by selection with these antitumor drugs. The drug-resistant cells were found to retain their potential for terminal differentiation induced by various inducers, such as a protein inducer in the conditioned medium of mouse L929 cells, dexamethasone, 1 alpha,25-dihydroxyvitamin D3, 2-[2-(dodecyloxy)ethoxy]ethyl 2-pyridinioethyl phosphate, and poly I. Differentiated cells showed morphological changes to mature macrophage-like cells, increase in phagocytic activity, and decrease in proliferative activity. Clonal analysis of M1-B24 cells showed that the cellular responses to the protein inducer of differentiation were not significantly different between drug-resistant clones selected with anti-tumor drugs and control (drug-sensitive) clones randomly isolated without selection. These results suggest that induction of differentiation of leukemic cells with the specific inducers is another approach to control the drug-resistant leukemia.
Hayashi
M
M
Okabe-Kado
J
J
Hozumi
M
M
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003561:Cytarabine / Q000627:therapeutic use*; D003630:Daunorubicin / Q000627:therapeutic use*; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011069:Poly I / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology
D009943:Organophosphorus Compounds; D011726:Pyridinium Compounds; D003561:Cytarabine; D008769:Methylnitronitrosoguanidine; D011069:Poly I; D003907:Dexamethasone; C046706:2(2-(dodecyloxy)ethoxy)ethyl-2-pyridioethyl phosphate; D002117:Calcitriol; D003630:Daunorubicin