Predicting Radiosensitivity Using DNA End-Binding Complex Analysis

Sheikh M. Ismail, Monica Puppi, Sheela Prithivirajsingh, Anupama Munshi, Uma Raju, Raymond E. Meyn, Thomas A. Buchholz, Michael D. Story, William A. Brock, Luka Milas, Howard D. Thames, Craig W. Stevens

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Previous reports have suggested that measuring radiosensitivity of normal and tumor cells would have significant clinical relevance for the practice of radiation oncology. We hypothesized that radiosensitivity might be predicted by analyzing DNA end-binding complexes (DNA-EBCs), which form at DNA double-strand breaks, the most important cytotoxic lesion caused by radiation. To test this hypothesis, the DNA-EBC pattern of 21 primary human fibroblast cultures and 15 tumor cell lines were studied. DNA-EBC patterns were determined using a modified electrophoretic mobility shift assay and were correlated with radiosensitivity, as measured by SF2. DNA-EBC analysis identified a rapidly migrating ATM-containing band (identified as "band-A") of which the density correlated with SF2 (0.02 ≤ SF2 ≤ 0.41) in primary fibroblasts (r2 = 0.77). The DNA-EBC pattern of peripheral blood lymphocytes was identical to that of fibroblasts. In addition, band-A density correlated with SF2 (0.35 ≤ SF2 ≤ 0.80) in 15 human tumor cell lines (r2 = 0.91). Densitometry of other bands, or total DNA-EBC binding, correlated more poorly with SF2 (r2 < 0.45). These data indicate that DNA-EBC analysis may be a practical, clinically relevant predictor of tumor and primary cell radiosensitivity.

Original languageEnglish (US)
Pages (from-to)1226-1234
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number4
DOIs
StatePublished - Feb 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Predicting Radiosensitivity Using DNA End-Binding Complex Analysis'. Together they form a unique fingerprint.

  • Cite this

    Ismail, S. M., Puppi, M., Prithivirajsingh, S., Munshi, A., Raju, U., Meyn, R. E., Buchholz, T. A., Story, M. D., Brock, W. A., Milas, L., Thames, H. D., & Stevens, C. W. (2004). Predicting Radiosensitivity Using DNA End-Binding Complex Analysis. Clinical Cancer Research, 10(4), 1226-1234. https://doi.org/10.1158/1078-0432.CCR-03-0331