Radiation-induced apoptosis in a murine lymphoma in vivo

A number of radiobiologic parameters of radiation-induced apoptosis were investigated in a syngeneic murine B-cell lymphoma, designated LY-TH. These included radiation dose effect, kinetics of apoptosis development, the effect of hypoxia and split-dose recovery. Tumors, 8 mm in size, were locally irradiated with graded doses ranging from 1 to 10-Gy gamma rays. Radiation-induced apoptosis was observed as early as 1 h after irradiation, peaked between 4 and 6 h and could no longer be detected 24 h later. The magnitude of the apoptotic response generally increased with radiation dose, but lower doses seemed to be relatively more effective than higher doses. Tumor hypoxia, produced by tumor clamping, inhibited induction of apoptosis by a factor of about 2.5. When two doses of radiation were separated by times of 1-10 days, the proportion of apoptotic cells induced by the second dose was greatly reduced compared to the initial dose. This reduction was the greatest when the second dose was given 2 days after the first dose. The proportion of apoptotic cells induced by the second dose slowly recovered after 2 days but it did not return to the initial levels after as long as 10 days.