High Oxygen Tension and Radiation Effect on the Kidney

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Abstract
Tissues that are well oxygenated have long been recognized as being more radiosensitive than those that are anoxic. Early experimental studies of the interaction between the tissue responses to irradiation and to oxygen were described by Crabtree and Cramer (1) and by Mottram (2). Read's (3) investigation with the broad bean root indicated that radio-sensitivity increased sharply with increasing oxygen concentrations when that concentration was low. At higher oxygen concentrations, further increase in the oxygen tension did not further add to radio-sensitivity. The radiosensitivity of a variety of biological tissues has now been shown to depend upon the concentration of oxygen present during the time of irradiation. The manner in which radiosensitivity varied with changes in oxygen pressure was described by Gray et al. (4) and by Gray (5). They showed that the administration of oxygen could greatly enhance the effectiveness of x-radiation in bringing about tumor regression. The tumor regression produced by 1,000 roentgens given while the animal was breathing oxygen approximately matched that due to a dose of between 1,500 and 2,000 roentgens when the animal was breathing air. Scott (4) also stated that, under the same conditions, damage to the skin was increased by only about 20 per cent by oxygen administration. These laboratory studies provided the stimulus for Churchill-Davidson et al. (6) to inaugurate a clinical program of irradiation of tumors in man under conditions of increased oxygen tension. Since then, similar clinical investigations have been initiated in a number of institutions. A review of the literature indicates that little is known of the interactions of radiation therapy and oxygen on well vascularized mammalian organs other than the skin, and a few reports have suggested that the combined use of the two agents might result in increased damage to normal well vascularized tissues (7). Moss (8) reported that with 7 per cent oxygen (atmospheric pressure) in the inhaled gas, 2,000 roentgens single dose, whole-chest irradiation produced barely perceptible epilation, while with the same radiation conditions and 100 per cent oxygen at 40 pounds pressure in the inhaled gas, a severe moist reaction occurred. It was believed, therefore, that an investigation should be undertaken to determine if injury to normal, well vascularized mammalian tissues was greater when they were irradiated under conditions of increased oxygen tension. The kidney was chosen for this study, as it is well vascularized, is moderately vulnerable to radiation injury (9–13), and there are numerous as well as sensitive tests available to quantitatively study alterations in renal function produced by irradiation. Mendelsohn and Caceres (13) studied roentgen-ray effects on renal function in dogs and found that alterations in glomerular filtration rate, renal blood flow, and TmPAH were roughly proportional to the dose of irradiation.

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