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Mechanistic insight...
Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure
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- Akuwudike, Pamela, 1987- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- López Riego, Milagrosa, 1992- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Ginter, Józef (author)
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- Cheng, Lei, 1981- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Wieczorek, Anna (author)
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Życieńska, Katarzyna (author)
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Łysek-Gładysińska, Małgorzata (author)
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- Wojcik, Andrzej, 1960- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Brzozowska, Beata (author)
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- Lundholm, Lovisa, 1978- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: DNA Repair. - 1568-7864 .- 1568-7856. ; 130
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Cells exposed to densely ionising high and scattered low linear energy transfer (LET) radiation (50 % dose of each) react more strongly than to the same dose of each separately. The relationship between DNA double strand break location inside the nucleus and chromatin structure was evaluated, using high-resolution transmission electron microscopy (TEM) in breast cancer MDA-MB-231 cells at 30 min post 5 Gy. Additionally, response to high and/or low LET radiation was assessed using single (1 ×1.5 Gy) versus fractionated dose delivery (5 ×0.3 Gy). By TEM analysis, the highest total number of γH2AX nanobeads were found in cells irradiated with alpha radiation just prior to gamma radiation (called mixed beam), followed by alpha, then gamma radiation. γH2AX foci induced by mixed beam radiation tended to be surrounded by open chromatin (lighter TEM regions), yet foci containing the highest number of beads, i.e. larger foci representing complex damage, remained in the heterochromatic areas. The γH2AX large focus area was also greater in mixed beam-treated cells when analysed by immunofluorescence. Fractionated mixed beams given daily induced the strongest reduction in cell viability and colony formation in MDA-MB-231 and osteosarcoma U2OS cells compared to the other radiation qualities, as well as versus acute exposure. This may partially be explained by recurring low LET oxidative DNA damage by every fraction together with a delay in recompaction of chromatin after high LET, demonstrated by low levels of heterochromatin marker H3K9me3 at 2 h after the last mixed beam fraction in MDA-MB-231. In conclusion, early differences in response to complex DNA damage may lead to a stronger cell kill induced by fractionated exposure, which suggest a therapeutic potential of combined high and low LET irradiation.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Radiation
- DNA damage
- DNA repair
- High LET
- Chromatin
- Mixed beam
Publication and Content Type
- ref (subject category)
- art (subject category)
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DNA Repair
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- By the author/editor
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Akuwudike, Pamel ...
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López Riego, Mil ...
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Ginter, Józef
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Cheng, Lei, 1981 ...
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Wieczorek, Anna
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Życieńska, Katar ...
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show more...
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Łysek-Gładysińsk ...
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Wojcik, Andrzej, ...
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Brzozowska, Beat ...
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Lundholm, Lovisa ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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DNA Repair
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Stockholm University