title: Cell inactivation by combined low dose-rate irradiation and intermittent hypoxia.
abstract: OBJECTIVE
  To investigate in detail the earlier observed combined effect of low dose-rate β-irradiation delivered at a dose-rate of 15 mGy/h and continued intermittent hypoxia that leads to extensive cell death after approximately 3-6 weeks.
  
  
  METHODS
  Continuous low dose-rate β-irradiation at a dose rate of 15, 1.5 or 0.6 mGy/h was given by incorporation of [(3)H]-labelled valine into cellular protein. The cells were cultivated in an atmosphere with 4% O2 using an INVIVO2 hypoxia glove box. Clonogenic capacity, cell-cycle distribution and cellular respiration were monitored throughout the experiments.
  
  
  RESULTS
  After 3-6 weeks most cells died in response to the combined treatment, giving a surviving fraction of only 1-2%. However, on continued cultivation a few cells survived and restarted proliferation as the cellular oxygen supply increased with the reduced cell number. Irradiating the T-47D cells grown in an atmosphere with 4% O2 at dose-rates 10 and 25 times lower than 15 mGy/h did not have a pronounced effect on the clonogenic capacity with surviving fractions of 60-80%.
  
  
  CONCLUSIONS
  Treatment of T-47D cells with low dose-rate β-irradiation leads to a specific effect on intermittent hypoxic cells, inactivating more than 98% of the cells in the population. Given improved oxygen conditions, the few surviving cells can restart their proliferation.
authors.affiliation: Department of Physics, University of Oslo , 0316 Oslo , Norway.
authors.forename: Nina Jeppesen
authors.initials: NJ
authors.lastname: Edin
authors.forename: Stine
authors.initials: S
authors.lastname: Christoffersen
authors.forename: Siri
authors.initials: S
authors.lastname: Fenne
authors.forename: Joe Alexander
authors.initials: JA
authors.lastname: Sandvik
authors.forename: Erik Olai
authors.initials: EO
authors.lastname: Pettersen
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded; D006801:Humans; D011829:Radiation Dosage
keywords: T-47D cells; hypoxia; low dose-rate irradiation; β-irradiation