title: Cytochrome-c mediated a bystander response dependent on inducible nitric oxide synthase in irradiated hepatoma cells.
abstract: BACKGROUND
  Radiation-induced bystander effect (RIBE) has important implication in tumour radiotherapy, but the bystander signals are still not well known.
  
  
  METHODS
  The role of cytochrome-c (cyt-c) and free radicals in RIBE on human hepatoma cells HepG2 was investigated by detecting the formation of bystander micronuclei (MN) and the generation of endogenous cyt-c, inducible nitric oxide (NO) synthase (iNOS), NO, and reactive oxygen species (ROS) molecules.
  
  
  RESULTS
  When HepG2 cells were cocultured with an equal number of irradiated HepG2 cells, the yield of MN in the nonirradiated bystander cells was increased in a manner depended on radiation dose and cell coculture time, but it was diminished when the cells were treated with cyclosporin A (CsA), an inhibitor of cyt-c release. Meanwhile the CsA treatment inhibited radiation-induced NO but not ROS. Both of the depressed bystander effect and NO generation in the CsA-treated cells were reversed when 5 μM cyt-c was added in the cell coculture medium. But these exogenous cyt-c-mediated overproductions of NO and bystander MN were abolished when the cells were pretreated with s-methylisothiourea sulphate, an iNOS inhibitor.
  
  
  CONCLUSIONS
  Radiation-induced cyt-c has a profound role in regulating bystander response through an iNOS-triggered NO signal but not ROS in HepG2 cells.
authors.affiliation: Institute of Radiation Medicine, Fudan University, No.2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: M
authors.initials: M
authors.lastname: He
authors.forename: S
authors.initials: S
authors.lastname: Ye
authors.forename: R
authors.initials: R
authors.lastname: Ren
authors.forename: C
authors.initials: C
authors.lastname: Dong
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.forename: D
authors.initials: D
authors.lastname: Yuan
authors.forename: C
authors.initials: C
authors.lastname: Shao
mesh_terms: D024201:Bystander Effect; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism*; D005720:Gamma Rays; D056945:Hep G2 Cells; D006801:Humans; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism; D015162:Micronucleus Tests; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D017382:Reactive Oxygen Species; D007550:Isothiuronium; D009569:Nitric Oxide; D016572:Cyclosporine; D045304:Cytochromes c; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C027744:S-methylisothiopseudouronium