Apoptotic death of lymphocytes upon treatment with 2-chloro-2'-deoxyadenosine (2-CdA).
In this work we addressed the question if the difference in the mechanism by which 2-CdA kills resting and proliferating cells could be responsible for the therapeutic window of the drug. We show that 2-CdA triggers programmed cell death in proliferating human promyelocytic cell line, HL-60, human lymphocytic cell line, MOLT-4, and human peripheral blood lymphocytes stimulated to proliferation by PHA. Under our experimental conditions 2-CdA failed to induce apoptosis in the resting human peripheral blood lymphocytes despite induction of massive apoptosis in the same lymphocytes stimulated to proliferation by PHA. We also show that 2-CdA-induced apoptosis in HL-60 and MOLT-4 cells can not be prevented by addition of nicotinamide or inhibiting poly(ADP-ribose) synthetase by 3-aminobenzamide. In the case of HL-60 cells apoptosis is specific to the S phase of the cell cycle. Taking together these data suggest that selective induction of apoptosis in proliferating cells may be responsible for the therapeutic value of 2-CdA.
Lassota
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P
Cancer Research Institute, New York Medical College, Elmsford 10523, USA.
Kazimierczuk
Z
Z
Darzynkiewicz
Z
Z
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D017338:Cladribine / Q000494:pharmacology* / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013268:Stimulation, Chemical; D014747:Vinblastine / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D010835:Phytohemagglutinins; D009243:NAD; D017338:Cladribine; D014747:Vinblastine; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases