The possible reduction in oxygen radiosensitization with decreasing radiation dose rate, offered as one reason for the excellent results of brachytherapy, has promoted suggestions that low dose rate radiation may be poor man's high LET radiation leading to possible circumvention of the oxygen effect in radiotherapy. However, opinions are not unanimous on the validity of OER reduction with dose rate decrease, due largely to artifacts possibly attendant in earlier experiments. It is proposed to systematically study the oxygen effect as a function of dose rate, and, as a function of oxygen concentration. Special experimental precautions, based on consideration of the potential artifacts, will be incorporated. The measured variation of OER, over a wide range of dose rates, will provide additional and perhaps more definitive data on this important question. In addition, study of OER at less than 40 rad/hr is of interest: if there is further OER decrease with dose rate below the clinical range, the use of lower dose rates may be suggested for brachytherapy in the hope of further minimizing the oxygen effect. The study of oxygen effect, under low dose rate conditions such that all sublethal damage is repaired, will yield information on the oxygen radiosensitization of single hit or lethal damage. Since single hit or lethal damage predominates in the initial portion of acute dose survival curves, the region of importance for fractionated radiotherapy, the above data, in contributing new insights relative to the oxygen radiosensitization above the shoulder region of the survival curve, will be of significant clinical interest. Further, examining radiosensitization as a function of pO2 at various dose rates in comparison with existing theoretical models will enhance the overall understanding of the basic mechanism of the oxygen effect. Insofar that cellular survival under low p02 levels and protracted radiation depends on oxygen radiosensitization as well as sublethal damage repair, it is planned to study split dose recovery kinetics of mammalian cells at low p02 levels. These parallel studies will yield important new information, basic to our knowledge of oxygen radiosensitization, and with potential implications for the understanding and improvement of radiotherapy.
