title: G(2)-M phase-correlative bystander effects are co-mediated by DNA-PKcs and ATM after carbon ion irradiation.
abstract: Accumulated evidence has shown that radiation-induced bystander effect (RIBE) may have significant implications to the efficiency of radiotherapy. Although cellular radiosensitivity relies on cell cycle status, it is largely unknown how about the relationship between RIBE and cell cycle distribution, much less the underlying mechanism. In the present study, the lung cancer A549 cells were synchronized into different cell cycle phases of G1, S and G2/M and irradiated with high linear energy transfer (LET) carbon ions. By treating nonirradiated cells with the conditioned medium from these irradiated cells, it was found that the G2-M phase cells had the largest contribution to RIBE. Meanwhile, the activity of DNA-PKcs but not ATM was increased in the synchronized G2-M phase cells in spite of both of them were activated in the asynchronous cells after carbon ion irradiation. When the G2-M phased cells were transferred with DNA-PKcs siRNA and ATM siRNA individually or treated with an inhibitor of either DNA-PKcs or ATM before carbon ion irradiation, the RIBE was effectively diminished. These results provide new evidence linking cell cycle to bystander responses and demonstrate that DNA-PKcs and ATM are two associated factors in co-regulating G2-M phase-related bystander effects.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Tu
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.affiliation: Research Development and Support Center, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Konishi
authors.affiliation: Research Development and Support Center, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
authors.forename: Alisa
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Research Development and Support Center, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.affiliation: Research Development and Support Center, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Uchihori
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China; Central Laboratory of Renji Hospital, Shanghai Jiaotong University, Shanghai 200001, China.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Bingrong
authors.initials: B
authors.lastname: Dang
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China. Electronic address: clshao@shmu.edu.cn.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics* / Q000378:metabolism; D024201:Bystander Effect; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects*; D045744:Cell Line, Tumor; D051747:DNA-Activated Protein Kinase / Q000235:genetics* / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase / Q000528:radiation effects; D005786:Gene Expression Regulation; D063193:Heavy Ion Radiotherapy / Q000379:methods*; D006801:Humans; D018499:Linear Energy Transfer; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance
chemical_list: D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human
keywords: ATM; Carbon ion; Cell cycle; DNA-PKcs; RIBE