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Chromatin- and temperature-dependent modulation of radiation-induceddouble-strand breaks
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences. (BMS)
2003 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, Vol. 79, no 10, 809-16 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To investigate the influence of chromatin organization and scavenging capacity in relation to irradiation temperature on the induction of double-strand breaks (DSB) in structures derived from human diploid fibroblasts. MATERIALS AND METHODS: Agarose plugs with different chromatin structures (intact cells+/-wortmannin, permeabilized cells with condensed chromatin, nucleoids and DNA) were prepared and irradiated with X-rays at 2 or 37 degrees C and lysed using two different lysis protocols (new ice-cold lysis or standard lysis at 37 degrees C). Induction of DSB was determined by constant-field gel electrophoresis. RESULTS: The dose-modifying factor (DMF(temp)) for irradiation at 37 compared with 2 degrees C was 0.92 in intact cells (i.e. more DSB induced at 2 degrees C), but gradually increased to 1.5 in permeabilized cells, 2.2 in nucleoids and 2.6 in naked DNA, suggesting a role of chromatin organization for temperature modulation of DNA damage. In addition, DMF(temp) was influenced by the presence of 0.1 M DMSO or 30 mM glutathione, but not by post-irradiation temperature. CONCLUSION: The protective effect of low temperature was correlated to the indirect effects of ionizing radiation and was not dependent on post-irradiation temperature. Reasons for a dose modifying factor <1 in intact cells are discussed.

Place, publisher, year, edition, pages
2003. Vol. 79, no 10, 809-16 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-65491DOI: 10.1080/09553000310001610204PubMedID: 14630540OAI: oai:DiVA.org:uu-65491DiVA: diva2:93402
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2009-07-28Bibliographically approved

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