Life span and thymic lymphoma incidence in high- and low-dose-rate irradiated AKR/J mice and commonly expressed genes.

To evaluate the effect of low-dose-rate radiation on cancer incidence, we housed AKR/J mice in a long-term low-dose-rate irradiation facility ((137)Cs, 0.07 cGy/h). We compared the thymic lymphoma incidence and life span with those of mice irradiated at a high dose rate ((137)Cs, 0.8 Gy/min, total dose of 4.5 Gy) and nonirradiated mice. The average life span of the low-dose-rate irradiated mice (243 days) was longer than those of the high-dose-rate irradiated mice (208 days) and nonirradiated mice (230 days) (P = 0.02). The incidence of thymic lymphoma in low-dose-rate irradiated mice was lower than that in nonirradiated mice and high-dose-rate irradiated mice by 10 and 20%, respectively (P < 0.01). Normal-sized thymuses were collected 130 days after irradiation, and whole genome microarray analysis was performed. A total of 17,625 genes were assessed. Up- and down-regulated genes in low-dose-rate irradiated mice were 1.7 and 9 times less frequent than in high-dose-rate irradiated mice. We profiled expressed genes associated with carcinogenesis pathways (DNA repair, DNA damage signaling pathway, cell cycle, cancer pathway finder, p53 signaling pathway, apoptosis and T-cell and B-cell activation). Apoptosis- (Cd5l, Fcgr3 and Pycard) and immune- (Pycard, Lilrb3, Igh-6, Fcgr2b and MGC60843) related genes were commonly activated in both high- and low-dose-rate irradiated mice. The results suggest that carcinogenic cells have been removed by activated apoptosis and immune mechanisms, contributing to decreased thymic lymphoma and elongated life span. Functional studies for expressed genes associated with thymic lymphoma incidence in low-dose-rate exposed mice are currently under way.