Prediction of clonogenic cell survival curves based on the number of residual DNA double strand breaks measured by gammaH2AX staining

Int J Radiat Biol. 2009 Nov;85(11):1032-41. doi: 10.3109/09553000903242149.

Abstract

Purpose: To assess the potential of using the residual phosphorylation of histone H2AX (gammaH2AX) after irradiation as a marker of radiosensitivity in vitro.

Material and methods: Confluent cell cultures of FaDu and SKX human squamous cell carcinoma lines were irradiated with graded single doses. Twenty-four hours after irradiation cells were seeded for standard colony forming assay (CFA). In parallel, staining for gammaH2AX was performed to visualise the residual foci.

Results: In the CFA, FaDu showed a higher radioresistance than SKX. After analysis of the residual foci data, we constructed 'predicted' survival curves using two different methods. First, the proportion of nuclei with <3 foci was found to correlate closely with the observed surviving fraction (SF) in FaDu, with a slight overestimation of the true SF in SKX. Second, there was a strong linear correlation of the mean number of residual foci and observed -lnSF. Based on regression analysis, we calculated the SF for both cell lines based on the mean number of residual gammaH2AX foci. This second approach again led to a good correlation of predicted and observed SF values in FaDu and a (slight) overestimation in SKX.

Conclusion: In the two cell lines investigated the mean number of residual foci of gammaH2AX can be used to predict differences in the radiation dose response relationship in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • DNA Breaks, Double-Stranded*
  • DNA, Neoplasm / radiation effects
  • Dose-Response Relationship, Radiation
  • Histones / metabolism*
  • Humans
  • Immunohistochemistry
  • Radiation Tolerance
  • Tumor Stem Cell Assay

Substances

  • DNA, Neoplasm
  • H2AX protein, human
  • Histones