The induction of apoptosis by chemotherapeutic agents occurs in all phases of the cell cycle.
A1.1 T-cell hybridoma cells exposed to either actinomycin D (1 microgram/ml), camptothecin (200 ng/ml) or aphidicolin (10 micrograms/ml) for 16 hrs at 37 degrees C die via apoptosis. The cell death was independent of RNA synthesis, in contrast to previous data reported for other forms of apoptosis in murine lymphocyte cells and their derived lines. Each of the three agents described appeared to induce death in all phases of the cell cycle in asynchronously proliferating cells. G1 cells appeared to be more susceptible to the effects of camptothecin and contrasts with other reports which detail its selectivity for S and G2 phase cells. This might indicate that cells are progressing into S phase before dying or, alternatively, cells may indeed be dying in G1. When elutriated synchronised cells were exposed to each of the three cytotoxic agents cell death occurred in all phases of the cell cycle. In view of the fact that G1 and S phase cells did not cycle to any appreciable extent during drug exposure, it was likely that ensuing death, occurred specifically from these phases. G2/M cells, however, moved rapidly into G1 in the presence of each drug, thus making it difficult to determine whether G2/M cells were capable of undergoing drug-induced apoptosis. To overcome this problem, nocodazole (50 ng/ml) was used to block asynchronous cells in M phase. When these cells were exposed to actinomycin D, aphidicolin or camptothecin, cell death ensued via apoptosis.
Cotter
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TG
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, CA 92037.
Glynn
J M
JM
Echeverri
F
F
Green
D R
DR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016590:Aphidicolin / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D006825:Hybridomas; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology; D013601:T-Lymphocytes
D000970:Antineoplastic Agents; D003609:Dactinomycin; D016590:Aphidicolin; D015739:Nocodazole; D002166:Camptothecin