RADIATION-INDUCED APOPTOSIS IN SENSITIVE AND RESISTANT CELLS ISOLATEDFROM A MOUSE LYMPHOMA

Cells were isolated from a mouse lymphoma (LY-TH) and grown in vitro. They were susceptible to radiation-induced apoptosis after low doses w ith the appearance of endonucleolytically fragmented DNA 1 h after irr adiation. Four hours after receiving 5 Gy, 80% of the DNA was endonucl eolytically cleaved. Apoptosis induction by DNA double-strand break (d sb) formation was more effective compared with induction by single-str and break (ssb) formation. After long-term culturing, LY-TH cultures b ecame refractory to apoptosis. Apoptosis-permissive cells (LY-as, clon ed from LY-TH cells) were three times more radiosensitive than clonall y expanded apoptosis-refractory cells (LY-ar). Low dose-rate irradiati on 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 t he initial phase of dsb rejoining. After 1 h, however, relative dsbs i n the LY-as variant increased as endonucleolytic cleavage was initiate d. Signalling for radiation-induced apoptosis in LY-as cells was indep endent of the DNA dsb repair pathway and appeared determined by initia l events, whereas in LY-ar cells, because of an inhibition in the apop totic pathway, survival was enhanced and modifiable by repair processe s.