Radioresistance of human tumor xenografts: possible mechanisms.

Cells of three human tumors irradiated in situ in athymic nude mice are more radioresistant at all doses than are corresponding cells irradiated in vitro. The tumors investigated were Na11 melanoma and two colorectal adenocarcinomas, HRT18 and HT29. While the Na11 tumor contains an exceptionally large hypoxic fraction, this is not true for the other two tumors, and other mechanisms have been proposed to explain these findings. Results of experiments described here suggest that the effect is not dependent on intercellular contact or on the age distribution of the cells in vivo. Tumor cells irradiated in situ were sensitized by both high-pressure oxygen and misonidazole, and the effect of the two agents together was greater than that of either used alone. It is concluded from the shape of the survival curve and from the response to high-pressure oxygen and/or misonidazole that the tumor cell population contains cells ranging from acutely hypoxic to fully oxygenated and includes a subpopulation of partially hypoxic cells of intermediate radiosensitivity.