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Radiation Research

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Radiation Research 154(6):680-685. 2000
doi: 10.1667/0033-7587(2000)154[0680:POTIDB]2.0.CO;2

Prevention of Type I Diabetes by Low-Dose Gamma Irradiation in NOD Mice

Mareyuki Takahashi¹ ^a, Shuji Kojima^b, Kiyonori Yamaoka^c, and Etsuo Niki^a

^aResearch Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan

^bResearch Institute for Biosciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278-0022, Japan

^cBioscience Department, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae, Tokyo 201-0004, Japan

¹Author to whom correspondence should be addressed at Research Institute for Biosciences, Science University of Tokyo, 2669 Yamazaki, Noda-shi, Chiba 278-0022, Japan.

Abstract

Takahashi, M., Kojima, S., Yamaoka, K. and Niki, E. Prevention of Type I Diabetes by Low-Dose Gamma Irradiation in NOD Mice.

Pretreatment with nonlethal, low-dose irradiation has been shown to have a protective effect against oxidative injury in animal tissues. Since oxidative injury of tissues is known to be a major cause of many human diseases, we examined the effect of low-dose irradiation on the progression of type I diabetes in mice. Nonobese diabetic (NOD) mice were treated with γ irradiation and the progression of the disease was monitored. An elevated level of glucose in urine was first detected at 15 weeks of age in the control NOD mice, whereas the detection was delayed as long as 7 weeks when the mice received a single dose of 0.5 Gy total-body irradiation between 12 and 14 weeks of age. The greatest effect was observed in the mice irradiated at 13 weeks of age. The increase in blood glucose and decrease in blood insulin were effectively suppressed by irradiation at 13 weeks of age. Both suppression of cell death by apoptosis and an increase in superoxide dismutase (SOD) activity were observed in the pancreas 1 week after irradiation. The results indicate that treatment with 0.5 Gy γ rays suppresses progression of type I diabetes in NOD mice. This is the first report on the preventive effect of low-dose irradiation on disease progression.

Received: February 29, 2000; Accepted: August 1, 2000

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FIG. 1. Effect of single-dose irradiation on the incidence of diabetes in female NOD mice. Mice were irradiated at 12, 13 and 14 weeks of age with 0.5 Gy γ rays. Untreated control mice were sham-irradiated at 13 weeks of age. The incidence of diabetes was monitored by detection of urine glucose exceeding 14 mmol/liter. Diabetes-free survival was analyzed by the Kaplan-Meier method

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FIG. 2. Effect of low-dose irradiation on the blood levels of biochemical markers of diabetes in female NOD mice. Mice were irradiated with 0.5 Gy γ rays at 12, 13 or 14 weeks of age. Untreated control mice were sham-irradiated at 13 weeks of age. Levels of markers were assayed at 22 weeks of age. Values are means ± SD. Ten mice were included in each group. *P < 0.005 by a paired t test between the control group and the irradiated group

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FIG. 3. Effect of two doses of radiation on the incidence of diabetes in female NOD mice. Mice were irradiated with 0.5 Gy γ rays at 12 and 13 weeks, 13 and 14 weeks, or 14 and 15 weeks of age (e.g., “13/14” represents irradiation at 13 and 14 weeks of age) with 0.5 Gy γ rays. Untreated control mice were sham-irradiated twice at 13 and 14 weeks of age. The incidence of diabetes was monitored by detection of urine glucose at 14 mmol/liter. Diabetes-free survival was evaluated by the Kaplan-Meier method

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FIG. 4. Detection of apoptotic cells in the pancreas of female NOD mice and suppression of apoptosis by irradiation with 0.5 Gy γ rays. Mice were irradiated (panel B) or sham-irradiated (panel A) at 13 weeks of age. Sample sections were prepared at 14 weeks of age and apoptotic cells were stained using the TUNEL method as described in the Materials and Methods. The arrow in panel A shows the formation of apoptotic bodies. Bar = 20 μm

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FIG. 5. Changes in SOD activity in the pancreas from female NOD mice after irradiation with 0.5 Gy γ rays. Mice were irradiated (irradiated) or sham-irradiated (untreated) at 13 weeks of age. Samples were prepared at 14 weeks of age for the assay of enzyme activity, which was performed as described in the Materials and Methods. Values are means ± SD. Ten mice were included in each group. *P < 0.005 by paired t test between the control group and the irradiated group