The induction of thymic lymphomas by whole-body X irradiation with four doses of 1.8 Gy (total dose: 7.2 Gy) in C57BL/6 mice was suppressed from a high frequency (90%) to 63% by preirradiation with 0.075 Gy X rays given 6 h before each 1.8-Gy irradiation. This level was further suppressed to 43% by continuous whole-body irradiation with 137Cs gamma rays at a low dose rate of 1.2 mGy/h for 450 days, starting 35 days before the challenging irradiation. Continuous irradiation at 1.2 mGy/h resulting in a total dose of 7.2 Gy over 258 days yielded no thymic lymphomas, indicating that this low-dose-rate radiation does not induce these tumors. Further continuous irradiation up to 450 days (total dose: 12.6 Gy) produced no tumors. Continuously irradiated mice showed no loss of hair and a greater body weight than unirradiated controls. Immune activities of the mice, as measured by the numbers of CD4+ T cells, CD40+ B cells, and antibody-producing cells in the spleen after immunization with sheep red blood cells, were significantly increased by continuous 1.2-mGy/h irradiation alone. These results indicate the presence of an adaptive response in tumor induction, the involvement of radiation-induced immune activation in tumor suppression, and a large dose and dose-rate effectiveness factor (DDREF) for tumor induction with extremely low-dose-rate radiation.

Chronic low-dose-rate radiation activated the immune system of the whole body.

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Effects of low-dose-rate gamma-irradiation on the process of tumorigenesis were investigated in mice treated with a carcinogenic agent or irradiated with high dose X-rays at a high dose rate. A prolonged gamma irradiation at approximately 1 mGy/hr suppressed the appearance of skin tumors induced by methylcholanthrene and delayed the appearance of radiation-induced thymic lymphomas in C57BL/6 mice. We also investigated the effects of low-dose-rate irradiation on disease model mice. In Type II diabetic C57BL/KsJ-db/db (db) mice, the urine glucose level was improved in some of the mice irradiated at 0.70 mGy/hr, but not in non-irradiated control mice. In MRL-lpr/lpr (lpr) mice with severe autoimmune diseases, immunological status was kept better in the mice irradiated at 0.35 or 1.2 mGy/hr. The incidence of a number of symptoms, including lymphadenopathy, splenomegaly and proteinuria, was suppressed by the irradiation. Furthermore, in both of the strains, the low-dose-rate irradiation prolonged the life span of the irradiated mice.

We examined the effect of the dihydropyridine calcium channel blocker (CCB) benidipine, the angiotensin II type 1 receptor blocker (ARB) candesartan, and the combination of these drugs on blood pressure and kidney and vascular function in rats with salt-induced hypertension. Dahl salt-sensitive (DS) rats were fed with a high-salt (8% NaCl) diet from 7 weeks of age. Benidipine (1, 3 mg/kg), candesartan (1, 3 mg/kg), benidipine