title: The bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality.
abstract: OBJECTIVE
  To investigate the dependence of the bystander cell-killing effect on radiation dose and quality, and to elucidate related molecular mechanisms.
  
  
  METHODS
  Normal human fibroblast WI-38 cells were irradiated with 0.125 - 2 Gy of γ-rays or carbon ions and were co-cultured with non-irradiated cells. Survival rates of bystander cells were investigated using the colony formation assays, and nitrite concentrations in the medium were measured using the modified Saltzman method.
  
  
  RESULTS
  Survival rates of bystander cells decreased with doses of γ-rays and carbon ions of ≤ 0.5 Gy. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of bystander cells. Moreover, nitrite concentrations increased with doses of less than 0.25 Gy (γ-rays) and 1 Gy (carbon ions). The dose responses of increased nitrite concentrations as well as survival reduction were similar between γ-rays and carbon ions. In addition, negative relationships were observed between survival rates and nitrite concentrations.
  
  
  CONCLUSIONS
  The bystander cell-killing effect mediated by NO radicals in normal human fibroblasts depends on irradiation doses of up to 0.5 Gy, but not on radiation quality. NO radical production appears to be an important determinant of γ-ray- and carbon-ion-induced bystander effects.
authors.affiliation: Microbeam Radiation Biology Group, Japan Atomic Energy Agency , Takasaki, Gunma , Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yokota
authors.forename: Tomoo
authors.initials: T
authors.lastname: Funayama
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mutou-Yoshihara
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D024201:Bystander Effect / Q000187:drug effects / Q000528:radiation effects*; D002244:Carbon / Q000009:adverse effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D018920:Coculture Techniques; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011829:Radiation Dosage; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors
chemical_list: D016166:Free Radical Scavengers; D009573:Nitrites; D009569:Nitric Oxide; D002244:Carbon
keywords: Bystander effect; carbon ion; cell killing; co-culture; nitric oxide; radiation quality