title: Role of ROS-mediated autophagy in radiation-induced bystander effect of hepatoma cells.
abstract: OBJECTIVE
  Autophagy plays a crucial role in cellular response to ionizing radiation, but it is unclear whether autophagy can modulate radiation-induced bystander effect (RIBE). Here, we investigated the relationship between bystander damage and autophagy in human hepatoma cells of HepG2.
  
  
  METHODS
  HepG2 cells were treated with conditioned medium (CM) collected from 3 Gy γ-rays irradiated hepatoma HepG2 cells for 4, 12, or 24 h, followed by the measurement of micronuclei (MN), intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and protein expressions of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 in the bystander HepG2 cells. In some experiments, the bystander HepG2 cells were respectively transfected with LC3 small interfering RNA (siRNA), Beclin-1 siRNA or treated with 1% dimethyl sulfoxide (DMSO).
  
  
  RESULTS
  Additional MN and mitochondrial dysfunction coupled with ROS were induced in the bystander cells. The expressions of protein markers of autophagy, LC3-II/LC3-I and Beclin-1, increased in the bystander cells. The inductions of bystander MN and overexpressions of LC3 and Beclin-1 were significantly diminished by DMSO. However, when the bystander cells were transfected with LC3 siRNA or Beclin-1 siRNA, the yield of bystander MN was significantly enhanced.
  
  
  CONCLUSIONS
  The elevated ROS have bi-functions in balancing the bystander effects. One is to cause MN and the other is to induce protective autophagy.
authors: Institute of Radiation Medicine, Fudan University , Shanghai , China.
authors: Xiangdong
authors: X
authors: Wang
authors: Jianghong
authors: J
authors: Zhang
authors: Jiamei
authors: J
authors: Fu
authors: Juan
authors: J
authors: Wang
authors: Shuang
authors: S
authors: Ye
authors: Weili
authors: W
authors: Liu
authors: Chunlin
authors: C
authors: Shao
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics; D001343:Autophagy / Q000528:radiation effects*; D000071186:Beclin-1; D024201:Bystander Effect / Q000528:radiation effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D005786:Gene Expression Regulation / Q000528:radiation effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species
keywords: ROS; Radiation; autophagy; bystander effect; mitochondrial dysfunction