High Expression of Circadian Gene mPer2 Diminishes Radiosensitivity of Tumor Cells

Objective: The aim of this study was to study mPeriod2 gene expression influencing the radiosensitivity of mouse tumor cells exposed to Co-60-gamma-rays. Materials and Methods: Lewis lung carcinoma (LLC) and EMT6 cells were induced by phorbol myristate acetate or transfected with pcDNA3.1-mPer2 and irradiated with (CO)-C-60-gamma-rays, then analyzed with several methods, such as flow cytometry, single-cell gel electrophoresis assay (SCGE), reverse-transcriptase polymerase chain reaction (RT-PCR), immunohisto-chemistry, chemistry, cell-clone-forming analysis, and so forth. Results: In SCGE analysis, the mPer2 high-expression groups exposed to gamma-rays presented lighter DNA damage, compared with controls (p < 0.05). Clone-forming efficiency and cell-survival curve showed that cells transfected with pcDNA3.1-mPer2 formed more clones than control groups and had augmented mean lethal dose (D-0), near field dose (Dq), decreasing extrapolation number (N), and a higher survival and clone-forming rate. RT-PCR analysis revealed a decreased expression of bax and p53, an increased expression of c-myc, bcl-2, and Rad51, and increased proportionality of bcl-2/bax, whereas p21 didn't change obviously in irradiated mper2-transfected LLC cells. Conclusions: This research suggests that the circadian system is involved in the protection and restoration of tumor cells against environmental detriments, such as Co-60-gamma-ray radiographic inspection. The gene, mPer2, might be considered as an inhibitor in tumor radiotherapy.