The specific aims of the proposed research are to examine the multifraction dose responses of several tissues whose injury is slowly expressed after radiotherapy. In particular our studies shall focus on the responses of arteries and arterioles, lung, skin, thyroid and brain. The investigations will be carried out in mice using radiobiological techniques some of which are well established, others of which are under development. The purpose of the experiments is to understand the pathobiology of these late injuries from radiation and to quantify the dose response relationships. Based on a better understanding of these late injuries it may be possible to devise treatment strategies that would minimize them and yet maintain or increase the effectiveness of radiation in eliminating cancerous tissues. With the development of high energy X-ray machines and protracted treatment regimens, the early responses of normal tissues to radiation can usually be circumvented and it is the late tissue injuries of the type to be studied which commonly limit the total dose, and therefore the probability of cancer control with modern radiotherapy.
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