The objective of the proposed research is to identify and quantify X-ray responses in tissues, with an overall goal of elucidating phenomena with potential for improving the effectiveness of radiation therapy for cancer. Recent evidence suggests that at the start of a radiation exposure, cells are highly sensitive but that small doses induce a repair capacity that increases their radioresistance. At present, the quantitation, and perhaps even the existence of this phenomenon, is open to question. The responses of kidney and vasculoconnective tissues to low doses of X rays will be accurately quantified to determine whether they exhibit an initial hypersensitive response before becoming more radioresistant as the dose increases. Low dose responses are of special interest in radiation oncology because small differences between tumors and normal tissues at low doses can be markedly amplified by repeated administration. The two tissues are clinically-important and their radiosensitivity to and recovery from multiple low doses given over time can be quantified without perturbation by repopulation or division cycle redistribution. The multifraction, low dose responses of the kidney will be measured using a clonogenic cell regrowth assay and 2 measurements of renal function. The response of the vasculoconnective tissue of the irradiated dermis will be measured by the tensile strength of wounds 14 days after surgical incision. The shape of the low dose response curves can be precisely reconstructed from multifraction responses which will permit identification and quantitation of initial hypersensitivity and a more resistant subsequent response, if they exist. An understanding of the magnitude and kinetics of induced radioresistance would facilitate investigation of mechanisms and possible exploitation of the phenomenon in clinical radiation therapy. A second, unrelated project will investigate the concept that certain tissues, notably the kidney, but also the vasculoconnective tissues of the dermis, will not tolerate reirradiation because radiation injury is progressive.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Radiation Study Section (RAD)
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University of California Los Angeles
Schools of Medicine
Los Angeles
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Withers, H R (2000) Biological aspects of conformal therapy. Acta Oncol 39:569-77
McBride, W H; Vegesna, V (2000) The role of T-cells in radiation pneumonitis after bone marrow transplantation. Int J Radiat Biol 76:517-21
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Chiang, C S; Hong, J H; Stalder, A et al. (1997) Delayed molecular responses to brain irradiation. Int J Radiat Biol 72:45-53

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