RP 1-11

Study of radiation-induced circulatory diseases using animal models


The Life Span Study (LSS) data indicate radiation-associated risk for hypertensive heart disease and stroke, and the Adult Health Study (AHS) data suggest radiation-associated risk for hypertension. We hypothesize that radiation may result in higher risk for circulatory diseases (CD). However, there are a limited number of animal model studies that have examined the relationship between radiation and CD at doses under 4 Gy, although some papers report that various biomarkers are affected by radiation. In this study, we propose the use of spontaneous hypertension rat-stroke prone (SHRSP) rats as rat CD models. Radiation doses from a brief single exposure will be given to the rats at 4, 2, and 1 Gy, with non-exposed (0 Gy) rats used as controls. We will evaluate acceleration of the development of hypertension in the SHRSP rats after radiation exposure. Moreover, we will measure candidate serum markers that have shown radiation dose effects based on previous AHS studies. In addition to serum markers, we will also measure 23 biomarkers in plasma samples by immunoassay. The priority of each plasma marker will be determined on the basis of previous results from AHS studies, and we plan to examine the effects of radiation exposure in morphological types in autopsy tissues by collaborating with the Institute for Environmental Sciences. This study will provide mechanistic information on the association between radiation exposure and development of CD.