title: Alpha particle-induced bystander effect is mediated by ROS via a p53-dependent SCO2 pathway in hepatoma cells.
abstract: OBJECTIVE
  The radiation-induced bystander effect (RIBE) has important implications for the efficiency of radiotherapy but the underlying role of cellular metabolism is widely unknown. The roles of synthesis of cytochrome c oxidase 2 (SCO2), a key effector for respiratory chain, and related signaling factors in α-particle-induced bystander damage were currently investigated in a liver cell co-culture system.
  
  
  METHODS
  Human hepatoma cells of HepG2 with wild-type p53 (wtp53) and Hep3B (p53 null) were irradiated with 0.4 Gy of α-particles and co-cultured with non-irradiated normal liver cells HL-7702 for 6 h, then the incidence of micronucleus (MN) in the bystander HL-7702 cells was analyzed. The expressions of total P53, phospho-P53 (p-P53), SCO2, and reactive oxygen species (ROS) in the irradiated hepatoma cells were detected. In some experiments, the hepatoma cells were respectively treated with p53 siRNA, SCO2 siRNA, or dimethyl sulfoxide (DMSO) before irradiation.
  
  
  RESULTS
  Bystander damage in HL-7702 cells was induced by α-irradiated HepG2 cells but not by α-irradiated Hep3B cells, and this bystander effect was diminished when the irradiated HepG2 cells were pretreated with p53 siRNA, SCO2 siRNA, or DMSO. Meanwhile, the expressions of p-P53 protein and SCO2 mRNA, the activity of SCO2 protein, and intracellular ROS were all increased in the irradiated HepG2 cells but not Hep3B cells and these expressions were eliminated by p53 siRNA treatment. Moreover, the radiation-enhanced expressions of SCO2 and ROS were inhibited by SCO2 siRNA.
  
  
  CONCLUSIONS
  α-particle-induced bystander effect was regulated by p53 and its downstream SCO2 in the irradiated hepatoma cells, and ROS generation could be an early event for triggering this bystander response.
authors.affiliation: Institute of Radiation Medicine, Fudan University , Shanghai , P. R. China.
authors.forename: Jitao
authors.initials: J
authors.lastname: Li
authors.forename: Mingyuan
authors.initials: M
authors.lastname: He
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D000512:Alpha Particles; D024201:Bystander Effect; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004579:Electron Transport; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D015162:Micronucleus Tests; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018832:Molecular Chaperones; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C400285:SCO2 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004121:Dimethyl Sulfoxide