Evidence for an Unconventional Radiosensitivity of Rat 9L Subcutaneous Tumors

The cellular radiosensitivity of rat 9L subcutaneous (sc) tumors was determined by measuring cell survival with an in vivo to in vitro colony-forming assay. The radiosensitivity of 9L tumor cells did not vary with changes in tumor weight (0.03-2.0 g), appearance of necrosis, or the use of anesthesia. None of the survival curves for cells from air-breathing rats had the traditional break normally associated with the presence of a hypoxic fraction. However, the composite survival curve showed a sensitivity ($D_{0}=3.6$ Gy) intermediate between and statistically different from that observed either for exponential cells from monolayer cultures ($D_{0}=1.8$ Gy) or single cells from dissociated tumors ($D_{0}=2.1$ Gy), and tumor cells from ${\rm N}_{2}\text{-asphyxiated}$ rats ($D_{0}=5.3$ Gy). There are four possible reasons for the intermediate radiosensitivity of in situ 9L sc tumors: (1) intercellular contact, (2) diffusion-limited phenomena, (3) perfusion-limited hypoxia, and (4) cellular recovery. This study indicates that either perfusion-limited hypoxia or more probably cellular recovery is the major contributor to the observed intermediate cellular radiosensitivity of 9L sc tumors.