L. M. van Putten

Effect of Pre-Irradiation on the Ratio of Oxygenated and Anoxic Cells in a Transplanted Mouse Tumor1

It is attractive to propose that the increased curative efficiency of radiation delivered by a fractionated scheme is greater than by single acute doses because of radiation-induced changes in the proportion or extent of anoxic regions within a tumor. Thus, early irradiation should tend preferentially to destroy those tumor cells which were located within a critical radius from capillaries and this would lead to a redistribution of oxygenated sites owing perhaps tp progressive passive migration of formerly anoxic foci to the radioresistant capillaries. Attempts to test this hypothesis directly by the implantation of oxygen-sensitive electrodes within tumors have been incapable of yielding reliable or unambiguous results. The present study was undertaken as an indirect approach to this question. Mice of the strain C3H/Km were inoculated subcutaneously with an isogenic transplanted sarcoma of spontaneous origin, and the tumors were allowed to grow for 10–14 days. Tumors were then irradiated in situ with 250 kv X-rays in either of two conditions: (a) in mice breathing air during irradiation, or (b) in mice which had been killed by nitrogen asphyxiation 5 minutes prior to the start of irradiation. Tumor cell surviving fractions were then obtained by endpoint dilution assay: the tumors were excised from their hosts, minced in Hanks’” solution, and made into a single cell suspension with the aid of mild trypsinization. The counted suspension was serially diluted in 5-fold steps and appropriate dilutions were inoculated into four separate subcutaneous sites in isogenic normal recipient mice (16 inocula/cell dilution). After scoring tumor takes in all sites for at least 100 days after in* On leave from: Radiobiological Institute of the Organization for Health Research T.N.O., Rijswijk (Z.H.), Netherlands. Sponsored by the Zellerbach Family Fund 57 oculation, estimates were made of the TD50, the number of cells necessary to produce a take (growth of a solid tumor at the site of inoculation) in 50 % of the cases in a given series of cell dilutions. By computing TD50 unirradiated/ TDhfj irradiated, survival curves were constructed. These survival curves were of the classic sigmoid shape and exhibites a D0 of 465 R (D10 = 1070 R). The survival curves of tumors irradiated in air-breathing mice and in dead mice had essentially the same terminal slopes, but significantly different O-dose extrapolates. If it is assumed that two extremes of radiosensitivity are exhibited by oxygenated vs. anoxic cells and that this sensitivity difference is the only one which is relevant to the present study, it may be deduced that approximately 15% of the cells of this tumor are anoxic in the air-breathing animal.The National Hospice Study of 1986 has not only revealed that hospices do a better job of meeting pain-control goals than do hospitals, but also elucidated a number of important differences in hospice and hospital care that account for this finding.