Modification of stromal radiosensitivity by misonidazole and WR-2721

The radiosensitivity of normal vascular connective tissue has been assessed by measuring the growth rate of untreated tumours implanted into pre-irradiated sites. Dose response curves have been constructed from two end-points, the latent period (time for the tumours to reach a diameter of 2 mm) and the growth rate in the macroscopic range (above 4 mm). Well defined dose response curves were obtained for both end-points, with a lower dose threshold for the macroscopic growth rate. A third end-point which combined the first two was also tested, i.e., time to reach 8 mm (23 to 76 days over the dose range tested). This was found to give the steepest dose response curves overall and was therefore judged to be the best assay. Modification of the radiosensitivity of stromal tissue by misonidazole and by WR-2721 was investigated using this assay. The dose response curve for X rays plus misonidazole was similar to that for X rays alone indicating little or no radiosensitisation. WR-2721, however, significantly reduced the X-ray response indicating radioprotection by a factor of 1.8 (range 1.4-2.7). These data show that tumour implantation is an effective way of eliciting a quantifiable response in previously irradiated stromal tissue. The assay allows resolution of dose differences as small as 1 to 2 Gy.