Antitumor Effects by Low Dose Total Body Irradiation

Abstract

Total-body irradiation (TBI) with 0.02-0.25 Gy has been reported to have antitumor effects. In mice, low-dose TBI induces tumor growth delay, antimetastatic effects, suppressive effects on the incidence of spontaneous thymiclymphoma, sensitization of tumor to ionizing radiation, and decrease in TD50 value. In artificial metastasis, 0.20 Gy TBI suppressed lung metastasis when it was conducted between 3 h before and 3 h after tumor cell injection into a tail vein. In spontaneous metastasis, 0.15-0.20 Gy TBI suppressed lung metastasis. Irradiation with 0.15 Gy twice a week from 11 weeks of age for 40 weeks significantly suppressed the incidence of spontaneous thymic lymphoma in AKR/J mice, which caused prolonged life span. Low-dose TBI has been used in the clinical treatment of lymphomatous malignancies including chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL). The usual practice was to give 0.1 Gy TBI three times a week or 0.15 Gy TBI two times a week to a total dose of 1.5 Gy. Despite this low total dose, low-dose fractionated TBI could induce long-term remissions and was as effective as the chemotherapy to which it was compared. Experimental data suggest that the antitumor effects of low-dose TBI could be explained by immune enhancement, induction of apoptosis, and intrinsic hypersensitivity to low-dose irradiation. Possible mechanisms of immune enhancement are elimination of the T-suppressor subset of lymphocytes and augmentation of the immune response including alteration of cytokine release and enhanced proliferative activity of lymphocytes to mitogenic stimuli.