title: High expression of circadian gene mPer2 diminishes radiosensitivity of tumor cells.
abstract: OBJECTIVE
  The aim of this study was to study mPeriod2 gene expression influencing the radiosensitivity of mouse tumor cells exposed to 60Co-gamma-rays.
  
  
  METHODS
  Lewis lung carcinoma (LLC) and EMT6 cells were induced by phorbol myristate acetate or transfected with pcDNA3.1-mPer2 and irradiated with 60Co-gamma-rays, then analyzed with several methods, such as flow cytometry, single-cell gel electrophoresis assay (SCGE), reverse-transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, 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 60Co-gamma-ray radiographic inspection. The gene, mPer2, might be considered as an inhibitor in tumor radiotherapy.
authors.affiliation: Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Yanyou
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Hua
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D002470:Cell Survival; D002940:Circadian Rhythm; D003037:Cobalt Radioisotopes / Q000494:pharmacology*; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D056950:Period Circadian Proteins; D011836:Radiation Tolerance; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D003037:Cobalt Radioisotopes; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate