title: Differential gene expression in human fibroblasts after alpha-particle emitter (211)At compared with (60)Co irradiation.
abstract: OBJECTIVE
  The aim of this study was to identify gene expression profiles distinguishing alpha-particle (211)At and (60)Co irradiation.
  
  
  METHODS
  Gene expression microarray profiling was performed using total RNA from confluent human fibroblasts 5 hours after exposure to (211)At labeled trastuzumab monoclonal antibody (0.25, 0.5, and 1 Gy) and (60)Co (1, 2, and 3 Gy).
  
  
  RESULTS
  We report gene expression profiles that distinguish the effect different radiation qualities and absorbed doses have on cellular functions in human fibroblasts. In addition, we identified commonly expressed transcripts between (211)At and (60)Co irradiation. A greater number of transcripts were modulated by (211)At than (60)Co irradiation. In addition, down-regulation was more prevalent than up-regulation following (211)At irradiation. Several biological processes were enriched for both irradiation qualities such as transcription, cell cycle regulation, and cell cycle arrest, whereas mitosis, spindle assembly checkpoint, and apoptotic chromosome condensation were uniquely enriched for alpha particle irradiation.
  
  
  CONCLUSIONS
  LET-dependent transcriptional modulations were observed in human fibroblasts 5 hours after irradiation exposure. These findings suggest that in comparison with (60)Co, (211)At has the clearest influence on both tumor protein p53-activated and repressed genes, which impose a greater overall burden to the cell following alpha particle irradiation.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. anna.danielsson@oncology.gu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Danielsson
authors.forename: Kristina
authors.initials: K
authors.lastname: Claesson
authors.forename: Toshima Z
authors.initials: TZ
authors.lastname: Parris
authors.forename: Khalil
authors.initials: K
authors.lastname: Helou
authors.forename: Szilárd
authors.initials: S
authors.lastname: Nemes
authors.forename: Kecke
authors.initials: K
authors.lastname: Elmroth
authors.forename: Jörgen
authors.initials: J
authors.lastname: Elgqvist
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
mesh_terms: D000512:Alpha Particles / Q000009:adverse effects*; D001246:Astatine / Q000009:adverse effects*; D002460:Cell Line; D003037:Cobalt Radioisotopes / Q000009:adverse effects; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D018499:Linear Energy Transfer / Q000528:radiation effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000528:radiation effects; D059467:Transcriptome / Q000528:radiation effects*
chemical_list: D003037:Cobalt Radioisotopes; D001246:Astatine