DEVELOPMENT OF APOPTOSIS IN IRRADIATED MURINE TUMORS AS A FUNCTION OF TIME AND DOSE

In a previous paper (Radiat. Res. 127, 308-316, 1991), we reported that a moderately radiosensitive, transplantable murine ovarian carcinoma (OCaI) displayed apoptosis after irradiation whereas a radioresistant hepatocellular carcinoma (HCaI) did not. These initial observations have been followed up in this detailed analysis of the development of apoptosis in these two tumors as a function of time and dose. Histological sections of OCaI and HCaI carcinomas were scored at various times between 0.5 and 24 h after single doses of 2.5 or 25 Gy γ radiation for the incidence of apoptosis. The percentage of nuclei undergoing apoptosis in untreated tumors was 5% in OCaI and 0.6% in HCaI. The peak in the number of apoptotic bodies occurred in the OCaI tumors 3-5 h after either dose. After 2.5 Gy, the peak incidence was about 20% and after 25 Gy it was about 30%. Irrespective of dose, HCaI tumors had an incidence of apoptosis of less than 3%. Based on the results of this time course, 4 h after irradiation was chosen for the determination of the dose response, over doses ranging from 2.5 to 25 Gy. The dose response for the OCaI tumors reached a plateau at 25-30% apoptotic nuclei after doses of about 7.5 Gy and above. Autoradiographic analysis of histological sections from mice injected with [3H]thymidine showed that some apoptotic bodies in the OCaI tumors arose from cycling cells. These results confirm that the apoptotic mode of cell death may represent an important response in some irradiated tumors.