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Oxygen effect for double-strand break induction determined by pulsed-field gel electrophoresis.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

  • Stephen J. Whitaker
  • Trevor J. McMillan
<mark>Journal publication date</mark>1992
<mark>Journal</mark>International Journal of Radiation Biology
Issue number1
Number of pages13
Pages (from-to)29-41
Publication StatusPublished
<mark>Original language</mark>English


The induction of DNA double-strand breaks (dsb) following irradiation under oxygenated and hypoxic conditions with and without misonidazole was measured by pulsed-field gel electrophoresis (PFGE) in a human bladder carcinoma cell line. The dose-response curve for DNA dsb detection by PFGE was biphasic with an apparent reduction in rate of dsb induced with dose. Oxygen enhancement ratios (OER) for cell survival (at a surviving fraction of 0·1) and for DNA damage assessed by PFGE (at 80% retained) were 2·0 and 3·0 respectively. Dose-modifying factors for misonidazole (15 mm), of 1·9 (survival) and 2·4 (DNA damage) were found. Although the magnitude of the inter-experiment variations limit the precision with which cell survival and DNA electrophoresis can be compared, the data do support a simple correlation between these two measures of response. When DNA dsb induction frequency was assessed from the number average molecular weight, values of 2·7 (±0·3), 0·7 (±0·1) and 2·6 (±0·5) × 10-9 dsb/bp/Gy were found for irradiation under oxic, hypoxic alone and hypoxic + misonidazole conditions respectively. This gives an OER of 3·9 and a DMF of 3·7.