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Chromatin organizat...
Chromatin organization contributes to non-randomly distributed double-strand breaks after exposure to high-LET radiation.
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Radulescu, Irina (author)
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- Elmroth, Kerstin, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för onkologi,Institute of Selected Clinical Sciences, Department of Oncology
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Stenerlöw, Bo (author)
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(creator_code:org_t)
- 2004
- 2004
- English.
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In: Radiation research. - 0033-7587. ; 161:1, s. 1-8
- Related links:
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https://gup.ub.gu.se...
Abstract
Subject headings
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- The influence of higher-order chromatin structure on the non-random distribution of DNA double-strand breaks induced by high-LET radiation was investigated. Five different chromatin structures (intact cells, condensed and decondensed chromatin, nucleoids and naked genomic DNA) from GM5758 cells or K562 cells were irradiated with (137)Cs gamma-ray photons and 125 keV/microm nitrogen ions (16-25 MeV/nucleon). DNA was purified with a modified lysis procedure to avoid release of heat-labile sites, and fragment size distributions and double-strand break yields were analyzed by different pulsed-field gel electrophoresis protocols. Whereas double-strand breaks in photon-irradiated cells were randomly distributed, irradiation of intact K562 cells with high-LET nitrogen ions produced an excess of non-randomly distributed DNA fragments 10 kb-1 Mbp in size. Complete removal of proteins eliminated this non-random component. There was a gradual increase in the yield of double-strand breaks for each chromatin decondensation step, and compared to intact cells, the yields for naked DNA (in buffer without scavengers) increased 83 and 25 times after photon and nitrogen-ion irradiation, respectively. The corresponding relative biological effectiveness decreased from 1.6-1.8 for intact cells to 0.49 for the naked DNA. We conclude that the organization of DNA into chromatin fiber and higher-order structures is responsible for the majority of non-randomly distributed double-strand breaks induced by high-LET radiation. However, our data suggest a complex interaction between track structure and chromatin organization over several levels.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Chromatin
- chemistry
- radiation effects
- DNA
- chemistry
- radiation effects
- DNA Damage
- Dose-Response Relationship
- Radiation
- Fibroblasts
- chemistry
- radiation effects
- Gamma Rays
- Heavy Ions
- Humans
- K562 Cells
- Linear Energy Transfer
- Molecular Weight
- Radiation Dosage
- Relative Biological Effectiveness
Publication and Content Type
- ref (subject category)
- art (subject category)
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