title: Differences in the kinetics of gamma-H2AX fluorescence decay after exposure to low and high LET radiation.
abstract: OBJECTIVE
  In order to obtain more insight into heavy ion tumour therapy, some features of the underlying molecular mechanisms controlling the cellular response to high linear energy transfer (LET) radiation are currently analysed.
  
  
  METHODS
  We analysed the decay of the integrated fluorescence intensity of gamma-H2AX (phosphorylated histone H2AX) which is thought to reflect the repair kinetics of radiation-induced DNA double-strand breaks (DSB) using Laser-Scanning-Cytometry. Asynchronous human HeLa cells were irradiated with a single dose of either 1.89 Gy of 55 MeV carbon ions or 5 Gy of 70 kV X-rays.
  
  
  RESULTS
  Measurements of the gamma-H2AX-intensities from 15-60 min resulted in a 16 % decrease for carbon ions and in a 43 % decrease for X-rays. After 21 h, the decrease was 77 % for carbon ions and 85 % for X-rays. The corresponding time-effect relationship was fitted by a bi-exponential function showing a fast and a slow component with identical half-life values for both radiation qualities being 24 +/- 4 min and 13.9 +/- 0.7 h, respectively. Apparent differences in the kinetics following high and low LET irradiation could completely be attributed to quantitative differences in their contributions, with the slow component being responsible for 47 % of the repair after exposure to X-rays as compared to 80 % after carbon ion irradiation.
  
  
  CONCLUSIONS
  gamma-H2AX loss kinetics follows a bi-exponential decline with two definite decay times independent of LET. The higher contribution of the slow component determined for carbon ion exposure is thought to reflect the increased amount of complex DSB induced by high LET radiation.
authors.affiliation: Klinikum rechts der Isar, Department of Radiation Oncology, Technische Universität München, München, Germany. T.E.Schmid@lrz.tu-muenchen.de
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Schmid
authors.forename: Günther
authors.initials: G
authors.lastname: Dollinger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Beisker
authors.forename: Volker
authors.initials: V
authors.lastname: Hable
authors.forename: Christoph
authors.initials: C
authors.lastname: Greubel
authors.forename: Susanne
authors.initials: S
authors.lastname: Auer
authors.forename: Anja
authors.initials: A
authors.lastname: Mittag
authors.forename: Attila
authors.initials: A
authors.lastname: Tarnok
authors.forename: Anna A
authors.initials: AA
authors.lastname: Friedl
authors.forename: Michael
authors.initials: M
authors.lastname: Molls
authors.forename: Barbara
authors.initials: B
authors.lastname: Röper
mesh_terms: D002244:Carbon; D002453:Cell Cycle; D053903:DNA Breaks, Double-Stranded; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D020450:Heavy Ions; D006657:Histones / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D018499:Linear Energy Transfer
chemical_list: C468783:H2AX protein, human; D006657:Histones; D002244:Carbon