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

Abstract

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 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 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 gamma rays is due to early death from a variety of neoplasms and not from increased incidence of specific neoplasms.

Alteration of Genome Structure Induced by Very Low Dose-Rate Irradiation in Mouse Tissues

“…Similar studies on mice irradiated with 414 mGy at a dose rate of 0.86 mGy/d (0.65 µGy/min) showed no detectable change. These characteristics correspond roughly to that observed for life-shortening (Tanaka, Tanaka, Sasagawa, Ichinohe, Takabatake, Matsushita, et al, 2003) and cancer-induction (Tanaka, Tanaka, Ichinohe, Matsushita, Matsumoto, Otsu, et al, 2007), suggesting a role of genomic alteration in radiation-induced cancer and/or life shortening.…”

“…These dose responses look similar to the effects on life shortening and cancer induction elucidated before under comparable conditions in B6C3 F1 mice (Tanaka, Tanaka, Sasagawa, Ichinohe, Takabatake, Matsushita, et al, 2003;Tanaka, Tanaka, Ichinohe, Matsushita, Matsumoto, Otsu, et al, 2007). It suggests a possible association between genomic alteration and life shortening and/or cancer induction.…”

Cytogenetic Instabilities in Atomic Bomb-Related Acute Myelocytic Leukemia Cells and in Hematopoietic Cells from Healthy Atomic Bomb Survivors

“…AB radiation might induce different type of cancer as well as cancer development with a shorter latency. A similar finding has been observed using analyses of array CGH and cell surface marker by FACS sorting for low-dose-rate radiation-induced murine leukemias, lymphomas and tumors by The Institute for Environmental Science (Tanaka et al, 2007;Hirouchi et al, 2009Hirouchi et al, , 2011). …”

Protein Sialylation by Sialyltransferase Involves Radiation Resistance

“…6), suggesting that ST6Gal I -mediated protein sialylation is involved in the radiation resistance response and protein sialylation enables the cell to resist radiation-induced damage through the inhibition of apoptosis. Ionizing radiation causes cancer and metastasis (57,58). Therefore, we are now examining the effects of radiation-induced increases in protein sialylation on adhesion and metastasis using sialylation site mutants of integrin h1.…”