Differential expression of cancer pathway-related genes in low-versus high-dose-rate-irradiated AKR/J mice

To understand the biological effects of ionizing radiation on lymphomagenesis, we reared AKR/J mice for 130 days with exposure to either high-dose-rate (HDR, 0.8 Gy/min, a single dose of 4.5 Gy) or low-dose-rate (LDR, 0.7 mGy/h, a cumulative dose of 2.1 Gy) irradiation. After 130 days, we compared the mean thymus weight, analyzed the histological changes, and measured apoptotic cell numbers using the terminal deoxynucleotidyl transferase-mediated dUTP-end labeling (TUNEL) assay. We also used microarrays and quantitative polymerase chain reaction analysis (qPCR) to analyze the expression profiles of cancer pathway-related genes in the thymuses of the mice. The mean thymus weight of the LDR-irradiated mice decreased relative to Sham- and HDR-irradiated mice. Histopathological examination revealed that the neoplastic cells in the thymuses of the Sham- and HDR-irradiated mice were pleomorphic, with marked anisocytosis and anisokaryosis, whereas the cells and their nuclei were relatively small and uniform in size in the LDR-irradiated mice. Furthermore, TUNEL assays showed that the number of apoptotic cells was higher in the LDR-irradiated mice than in the Sham- and HDR-irradiated mice. Microarray analysis showed differentially expressed genes according to carcinogenic stage (DNA repair/genomic instability, DNA damage signaling pathway, cell cycle, cancer pathway, p53 signaling pathway, apoptosis, and T- and B-cell activation). qPCR data for cancer pathway-related genes showed that Cds1 gene expression was upregulated in the LDR-irradiated mice, whereas expression of the Itga4, Myc, and Itgb1 genes was upregulated in the irradiated mice. However, the functions of cancer pathway-related genes require further study and validation.