Residual late radiation damage in mouse stromal tissue assessed by the tumor bed effect

Irradiation of murine subcutaneous stroma before implantation of tumor cells leads to retarded tumor growth. This effect is called Tumor Bed Effect (TBE) and can be used to assess the sensitivity of stromal tissue to radiation. We tested the ability of stromal tissue to recover from X-ray-induced damage as a function of the time interval between X-irradiation and implantation of tumor cells over a period of 195 days. We also assessed the effects of a second test treatment of X-irradiation before implantation to assess residual damage by the first radiation treatment. The tumor bed effect in C57Bl10xDBA2 mice observed after X-ray treatment and implantation of M8013 cells (from a transplantable mouse mammary carcinoma) declines with the time that elapses between X-rays and implantation. Implantation of tumor cells 195 days after initial irradiation of 10 or 20 Gy resulted in a considerably smaller TBE. The half-time of the decay is estimated as about 50 days. The extent of the recovery was then tested in two-fraction experiments, with radiation fractions separated by intervals of 30 or 180 days. In the experiment with re-irradiation at an interval of 30 days after the first radiation dose of 20 Gy hardly any recovery was observed, whereas at an interval of 180 days a considerable recovery was observed. We presume that the recovery in TBE that was observed a long time after the irradiation results from a proliferative stimulus to endothelial cells which takes place during the post-irradiation period. The proliferative response leads to cell death of the X-ray damaged endothelial cells and thereafter these are replaced by healthy cells.