MODULATION OF RADIATION-INDUCED APOPTOSIS AND G(2) M BLOCK IN MURINE T-LYMPHOMA CELLS/

Radiation-induced apoptosis in lymphocyte-derived cell lines is charac terized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DN A gel electrophoresis) and quantitatively (diphenylamine reagent assay ) in murine EL4 T-lymphoma cells exposed to Cs-137 gamma irradiation. Fragmentation was discernible within 18-24 h after exposure. It increa sed with time and dose and reached a plateau after 8 Gy of gamma radia tion. We studied the effect of several pharmacological agents on the r adiation-induced G(2)/M block and DNA fragmentation. The agents which reduced the radiation-induced G(2)/M-phase arrest (caffeine, theobromi ne, theophylline and 2-aminopurine) enhanced the degree of DNA fragmen tation at 24 h. In contrast, the agents which sustained the radiation- induced G(2)/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) i nhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-ind uced genetic damage are eliminated by apoptosis subsequent to a G(2)/M block. Furthermore, it may be possible to modulate the process of rad iation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G(2)/M block, and to use this effec t in the treatment of patients with malignant disease. (C) 1995 by Rad iation Research Society