Tanaka, I. B., III, Tanaka, S., Ichinohe, K., Matsushita, S., Matsumoto, T., Otsu, H., Oghiso, Y. and Sato, F. Cause of Death and Neoplasia in Mice Continuously Exposed to Very Low Dose Rates of Gamma Rays. Radiat. Res. 167, 417–437 (2007). Four thousand 8-week-old SPF B6C3F1 mice (2000 of each sex) were divided into four groups, one nonirradiated (control) and three irradiated. The irradiated groups were exposed to 137 Cs γ rays at dose rates of 21, 1.1 and 0.05 mGy day −1 for approximately 400 days with total doses equivalent to 8000, 400 and 20 mGy, respectively. All mice were kept until natural death, and pathological examination was performed to determine the cause of death. Neoplasms accounted for >86.7% of all deaths. Compared to the nonirradiated controls, the frequency of myeloid leukemia in males, soft tissue neoplasms and malignant granulosa cell tumors in females, and hemangiosarcoma in both sexes exposed to 21 mGy day −1 were significantly increased. The number of multiple primary neoplasms per mouse was significantly increased in mice irradiated at 21 mGy day −1 . Significant increases in body weights were observed from 32 to 60 weeks of age in males and females exposed to 1.1 mGy day −1 and 21 mGy day −1 , respectively. Our results suggest that life shortening (Tanaka et al., Radiat. Res. 160, 376–379, 2003) in mice continuously exposed to low-dose-rate γ rays is due to early death from a variety of neoplasms and not from increased incidence of specific neoplasms.
Tanaka, S., Tanaka, I. B. III., Sasagawa, S., Ichinohe, K., Takabatake, T., Matsushita, S., Matsumoto, T., Otsu, H. and Sato, F. No Lengthening of Life Span in Mice Continuously Exposed to Gamma Rays at Very Low Dose Rates. Radiat. Res. 160, 376–379 (2003). Late effects of continuous exposure to ionizing radiation are potential hazards to workers in radiation facilities as well as to the general public. Recently, low-dose-rate and low-dose effects have become a serious concern. Using a total of 4000 mice, we studied the late biological effects of chronic exposure to low-dose-rate radiation as assayed by life span. Two thousand male and 2000 female 8-week-old specific-pathogen-free (SPF) B6C3F1 mice were randomly divided into four groups (one nonirradiated control and three irradiated). Irradiation was carried out for approximately 400 days using 137 Cs γ rays at dose rates of 21 mGy day –1 , 1.1 mGy day –1 and 0.05 mGy day –1 with total doses equivalent to 8000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept under SPF conditions until they died spontaneously. Statistical analyses showed that the life spans of mice of both sexes irradiated with 21 mGy day –1 ( P < 0.0001) and of females irradiated with 1.1 mGy day –1 ( P < 0.05) were significantly shorter than those of the control group. Our results show no evidence of lengthened life span in mice continuously exposed to very low dose rates of γ rays.
The late effects of heavy-ion irradiation on the spinal cord of the rat were investigated histologically and morphometrically. After a single exposure of each animal's lower thoracic and lumbar spinal cord to a carbon-ion beam, the animals were observed clinically for up to 69 weeks and their spinal cords were examined histologically after sacrifice. Paralysis of the hind limbs appeared from 16 to 20 weeks after irradiation with 20 Gy or more. The first histological change seen was vacuolization in the marginal white matter, which appeared 19 to 25 weeks after irradiation with more than 10 Gy. After irradiation with more than 15 Gy, bilateral destructive cavities occurred in the white matter, especially in the lateral tract. These histological changes were similar to those reported frequently for X irradiation. The mean cross-sectional area of the blood vessels in the irradiated spinal cord increased in a manner that was dependent on dose and was significantly larger 15 to 17 weeks after irradiation with 30 Gy. Reconstruction of small destructive lesions from serial sections consistently revealed dilated veins in the centers of these lesions. The effective dose that induces 50% incidence of hind-limb paralysis and destructive cavity formation ( ED 50 ) as determined using a curve-fitting method was 18.5 and 19.5 Gy, respectively, and the latent period was shorter than that for X irradiation.