title: Differential bystander signaling between radioresistant chondrosarcoma cells and fibroblasts after x-ray, proton, iron ion and carbon ion exposures.
abstract: OBJECTIVE
  Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells.
  
  
  METHODS
  Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated.
  
  
  RESULTS
  In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells.
  
  
  CONCLUSIONS
  We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan. wa@mbe.nifty.com
authors.forename: Masaru
authors.initials: M
authors.lastname: Wakatsuki
authors.forename: Nicole
authors.initials: N
authors.lastname: Magpayo
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Kawamura
authors.forename: Kathryn D
authors.initials: KD
authors.lastname: Held
mesh_terms: D024201:Bystander Effect / Q000502:physiology / Q000528:radiation effects*; D002244:Carbon; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D018920:Coculture Techniques / Q000379:methods; D004249:DNA Damage; D004361:Drug Tolerance / Q000502:physiology / Q000528:radiation effects*; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D007501:Iron; D018499:Linear Energy Transfer; D015162:Micronucleus Tests; D011522:Protons; D011829:Radiation Dosage; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011522:Protons; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D002244:Carbon; D007501:Iron