title: Radiation-induced apoptosis in sensitive and resistant cells isolated from a mouse lymphoma.
abstract: Cells were isolated from a mouse lymphoma (LY-TH) and grown in vitro. They were susceptible to radiation-induced apoptosis after low doses with the appearance of endonucleolytically fragmented DNA 1 h after irradiation. Four hours after receiving 5 Gy, 80% of the DNA was endonucleolytically cleaved. Apoptosis induction by DNA double-strand break (dsb) formation was more effective compared with induction by single-strand break (ssb) formation. After long-term culturing, LY-TH cultures became refractory to apoptosis. Apoptosis-permissive cells (LY-as, cloned from LY-TH cells) were three times more radiosensitive than clonally expanded apoptosis-refractory cells (LY-ar). Low dose-rate irradiation and maintenance at 25 degrees C for 5 h postirradiation was sparing in LY-ar but not LY-as cells, suggesting a repair deficiency in LY-as cells. Analysis of dsb rejoining kinetics revealed no difference in the initial phase of dsb rejoining. After 1 h, however, relative dsbs in the LY-as variant increased as endonucleolytic cleavage was initiated. Signalling for radiation-induced apoptosis in LY-as cells was independent of the DNA dsb repair pathway and appeared determined by initial events, whereas in LY-ar cells, because of an inhibition in the apoptotic pathway, survival was enhanced and modifiable by repair processes.
authors: Department of Experimental Radiotherapy, M.D. Anderson Caner Center, Houston, TX 77030.
authors: M D
authors: MD
authors: Story
authors: D W
authors: DW
authors: Voehringer
authors: C G
authors: CG
authors: Malone
authors: M L
authors: ML
authors: Hobbs
authors: R E
authors: RE
authors: Meyn
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002470:Cell Survival; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
chemical_list: D004247:DNA