Gene expression profiles in mouse liver after long-term low-dose-rate irradiation with gamma rays.

Changes in gene expression profiles in mouse liver induced by long-term low-dose-rate gamma irradiation were examined by microarray analysis. Three groups of male C57BL/6J mice were exposed to whole-body radiation at dose rates of 17–20 mGy/day, 0.86–1.0 mGy/day or 0.042–0.050 mGy/day for 401–485 days with cumulative doses of approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively. The gene expression levels in the livers of six animals from each exposure group were compared individually with that of pooled sham-irradiated animals. Some genes revealed a large variation in expression levels among individuals within each group, and the number of genes showing common changes in individuals from each group was limited: 20 and 11 genes showed more than 1.5-fold modulation with 17–20 mGy/day and 0.86–1.0 mGy/day, respectively. Three genes showed more than 1.5-fold modulation even at the lowest dose-rate of 0.04–0.05 mGy/day. Most of these genes were down-regulated. RT-PCR analysis confirmed the expression profiles of the majority of these genes. The results indicate that a few genes are modulated in response to very low-dose-rate irradiation. The functional analysis suggests that these genes may influence many processes, including obesity and tumorigenesis

Cause of Death and Neoplasia in Mice Continuously Exposed to Very Low Dose Rates of Gamma Rays

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 137Cs gamma 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 neoplasmas 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 obseved 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 gamma rays is due to early death from a variety of neoplasms and not from increased incidence of specific neoplasms