A major research effort is to study the response to fractionated irradiation of xenografts of human astrocytoma (high grade), squamous cell carcinoma, and mammary adenocarcinoma growing in nude mice. The end-point is to be the dose which achieves a specified growth delay. Radiation is to be given in 1, 2, 4, and 10 equal doses under clamp hypoxic conditions. To decrease the level of immune rejection against the xenografts, the nude mice will be prepared by procedures to immune suppress and to induce specific tolerance (partial or hopefully complete). An important component of this work will be to evaluate several procedures, alone and in combination, designed to immune suppress and to induce specific tolerance in the nude mouse. Evaluation of the radiation response data will be in terms of Alpha/Beta and Alpha/e ratios derived from plots of the reciprocal of dose which produces a specified delay in tumor growth against dose per fraction (an Fe plot). An additional set of experiments will be to examine for the extent of PLDR (potentially lethal damage repair) by comparing the cell number to transplant the tumor for tumor excised immediately or 6 hours after single dose irradiation. In addition Alpha/Beta amd Alpha/e are to be determined for a spontaneous fibrosarcoma two spontaneous squamous cell carcinoma and an ovarian carcinoma using early generation isotransplants in the C3Hf/Sed mouse. Another major area of research will be the examination for correlations between tumor response and biochemically determined levels of lactate, the Krebs cycle intermediates, and the adenylate nucleotides from small biopsy samples (less than 20mg) before and at mid-point during fractionated irradiation (Upsilon=10). The determination will be made using HPLC techniques. Parallel experiments will be made for polarographically estimated tissue P02 (using a simple electrode system, measurements at 3-4 points. A similar experiment will determine intertumor variation in adriamycin concentration (HPLC technique, small biopsy specimen) and also examine for correlation between tumor response to adriamycin alone or with radiation. This series is to be made on isotransplants and spontaneous autochthonous tumors. Also, a study will be made of effect of procedures to suppress Q02 to modify tumor response to radiation given to Air or 023ATA respiring mice.
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