Radiation can cause decreased tissue integrity and poor wound healing over the long-term due to vascular damage. Radiation-damaged tissue is poorly oxygenated because of an inadequate blood supply. Hypoxia usually stimulates compensatory angiogenesis leading to improved oxygenation. However, in tissues with late radiation damage, the gradient of oxygen across the irradiated field is hypothesized to be so shallow that angiogenesis is not stimulated. Hyperbaric oxygen (HB02) is a well established alternative modality for the treatment of many late radiation effects and has been shown to increase angiogenesis in poorly vascularized tissues; however, the mechanism by which this occurs is poorly understood. We propose to rigorously test the hypothesis that HB02 treatment of irradiated tissues leads to the establishment of a steeper oxygen gradient, causing influx of macrophages into the hypoxic areas and release of angiogenic factors resulting in increased angiogenesis. In contrast to normal tissues, HB02 treatment has been anecdotally reported to promote tumor growth. Such reports have not been scientifically validated or refuted. We therefore propose to examine the effects of HB02 on the growth of tumors. Since HB02 therapy is used to mitigate radiation-induced damage, the effect of post irradiation HB02 treatment on the growth of tumors will be examined. At the same time we will document changes in tumor angiogenesis and oxygenation by HB02 using both immunocytochemical and non-invasive monitoring. These studies will better define the mechanism of HB02 action on both normal and tumor tissues.
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