Modification of stromal radiosensitivity by misonidazole and WR-2721

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Abstract
The radiosensitivity of normal vascular connective tissue was assessed by measuring the growth rate of untreated tumors [mouse adenocarcinoma CA NT cells] implanted into pre-irradiated sites. Dose response curves were constructed from 2 end-points, the latent period (time for the tumors 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 3rd end-point which combined the first 2 was also tested, i.e., time to reach 8 mm (23 to 76 days over the dose range tested). This gave the steepest dose response curve overall and was therefore judged to be the best assay. Modification of the radiosensitivity of stromal tissue by misonidazole and by WR-2721 [S-2-(aminopropyl-amino)ethylphosphorothoic acid] 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 radiosensitization. WR-2721, however, significantly reduced the X-ray response indicating radioprotection by a factor of 1.8 (range 1.4-2.7). Tumor 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 1-2 Gy [gray].

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