RP 2-12

A study of circulatory diseases using animal models irradiated with lower doses (Addendum to RP 1-11)


The Life Span Study (LSS) data indicate that there are radiation-associated risks for hypertensive heart disease and stroke, and the Adult Health Study (AHS) data suggest there are radiation-associated risks for hypertension. We hypothesize that radiation may result in a higher risk for circulatory diseases (CD), and we started a study using the stroke-prone spontaneous hypertensive rat (SHRSP) as a CD animal model. In the study of RP 1-11, radiation doses from a brief single exposure were given to the rats (1, 2, and 4 Gy, with non-exposed [0 Gy] rats used as controls). The results suggested that the life span of irradiated rats decreased with statistical significance compared to the control rats. We also evaluated radiation effects for morphological and pathological phenotypes in collaboration with the Institute for Environmental Sciences. The results showed that the phenotypic changes observed in the organs (brain, heart, and kidney) of irradiated rats were more severe than those observed in the organs of control rats. Thus, our results suggest that additional studies in which the rats are irradiated with less than 1 Gy may be an opportunity for providing us with additional interesting data. The purpose of this addendum RP using SHRSP rats is that we will evaluate CD radiation effects focusing on lower-dose radiation exposure (1 Gy) in rats by examining morphological and pathological phenotypes and measuring the same blood biomarkers as used in the original RP. In addition to the above, we plan to examine the effects of lower-dose radiation exposure on the life span of SHRSP rats.

The second purpose of this addendum is to evaluate acceleration of the development of hypertension in spontaneous hypertensive rats (SHR) after radiation exposure (0 Gy to 4 Gy). In the previous study using SHRSP rats, we could not measure blood pressure after SHRSP rats showed the first stroke symptoms, since we were concerned that the measurement of blood pressure might cause the next stroke symptoms in the rats. We will also conduct the same examinations in the SHR rats as in the SHRSP study. The SHR rat study will be able to provide more information on the association between radiation exposure and development of CD.