Suppression of thymic lymphoma induction by life-long low-dose-rate irradiation accompanied by immune activation in C57BL/6 mice.
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.
Ina
Yasuhiro
Y
Low Dose Radiation Research Center, Central Research Institute of Electric Power Industry, 2-11-1 Iwado-kita, Komae, Tokyo, 201-8511, Japan.
Tanooka
Hiroshi
H
Yamada
Takeshi
T
Sakai
Kazuo
K
D000222:Adaptation, Physiological / Q000528:radiation effects; D000818:Animals; D001822:Body Burden; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008223:Lymphoma / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000528:radiation effects*; D013953:Thymus Neoplasms / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D014916:Whole-Body Irradiation / Q000009:adverse effects* / Q000379:methods