RADIATION STUDIES IN VASCULAR AND LYMPHATIC TISSUE

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IN VIVO: Using the Sandison-Clark rabbit ear chamber microvascular model in New Zealand white male rabbits sequential in vivo observations will be made on the mature microvasculature and lymphatic channels to evaluate the effects of radiation. The following parameters are studied: 1) vascular lengh, 2) vascular surface area, 3) vascular volume, 4) intervessel distance or vascular density and 5) vessel wall thickness as a function of dose and time after injury. Radiation will be small single doses, up to 200 rads, fractionated doses and hyperfractionation and by continuous radiation. Quantitative and qualitative criteria will be used to analyze the extent of injury and repair in arterioles, capillaries, and venules. Late effects are the main objective of this investigation. Lymphatic vessels injury will be quantitated for early and intermediate effects using the same methodology and parameters. IN VITRO: Studies comparing primary cultures, sub-cultures and wounded cultures of endothelial cells, smooth muscle cells and vascular fibroblasts will be carried out to provide predictive information for the in vivo experiments. Alternatively, donor tissue is irradiated in vivo in rabbits and will be scored in vitro in tissue culture. Determination of late effects on cell cultures will be carried out. From these studies we intend to correlate late injury of blood vessels and lymphatic late tissue injury of patients documented in the literature. These studies schould provide the radiotherapist with the information leading to development of treatment strategies which will minimize late vascular and lymphatic injury and decrease morbidity in cancer management.