title: RBE of α-particles from (211)At for complex DNA damage and cell survival in relation to cell cycle position.
abstract: OBJECTIVE
  To investigate cell cycle effects and relative biological effectiveness (RBE) of α-particles from the clinically relevant radionuclide Astatine-211 ((211)At), using X-rays as reference radiation. Double-strand breaks (DSB), non-DSB clusters containing oxidised purines and clonogenic survival were investigated.
  
  
  METHODS
  Asynchronous V79-379A fibroblasts or cells synchronised with mimosine in G1, early, mid and late S phase or in mitosis were irradiated with X-rays (100 kV(p)) or (211)At (mean linear energy transfer (LET) 110 keV/μm). Induction of DSB and clusters was determined using pulsed-field gel electrophoresis with fragment analysis. Cell survival was obtained with the clonogenic assay.
  
  
  RESULTS
  In asynchronous cells RBE for DSB- and cluster-induction was 3.5 and 0.59, respectively. RBE for 37% cell survival was 8.6. In different cell cycle phases RBE varied from 1.8-3.9 for DSB and 3.1-7.9 for 37% survival (survival at 2 Gy was 6.9-38 times lower after α-irradiation). (211)At induced 6 times more DSB and X-rays induced 11 times more DSB in mitotic cells with highly compacted chromatin relative G1.
  
  
  CONCLUSIONS
  The radio-response is cell cycle dependent and differs between proliferating and non-cycling cells for both low- and high-LET radiation, resulting in a variation in RBE of α-particles between 1.8 and 8.6.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Claesson
authors.forename: Karin
authors.initials: K
authors.lastname: Magnander
authors.forename: Helena
authors.initials: H
authors.lastname: Kahu
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
authors.forename: Kecke
authors.initials: K
authors.lastname: Elmroth
mesh_terms: D000186:Actinium; D000512:Alpha Particles; D000818:Animals; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects*; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness
chemical_list: D004247:DNA; D000186:Actinium