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Quantitative γ-H2AX...
Quantitative γ-H2AX immunofluorescence method for DNA double-strand break analysis in testis and liver after intravenous administration of 111InCl3
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- Stenvall, Anna (author)
- Lund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,Systemic Radiation Therapy Group,Lund University Research Groups
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- Larsson, Erik (author)
- Skåne University Hospital
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- Holmqvist, Bo (author)
- ImaGene-iT AB
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- Strand, Sven Erik (author)
- Lund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Jönsson, Bo Anders (author)
- Lund University,Lunds universitet,Nuclear Medicine Physics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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(creator_code:org_t)
- 2020-03-19
- 2020
- English.
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In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 10:1
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Abstract
Subject headings
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- Background: It is well known that a severe cell injury after exposure to ionizing radiation is the induction of DNA double-strand breaks (DSBs). After exposure, an early response to DSBs is the phosphorylation of the histone H2AX molecule regions adjacent to the DSBs, referred to as γ-H2AX foci. The γ-H2AX assay after external exposure is a good tool for investigating the link between the absorbed dose and biological effect. However, less is known about DNA DSBs and γ-H2AX foci within the tissue microarchitecture after internal irradiation from radiopharmaceuticals. Therefore, in this study, we aimed to develop and validate a quantitative ex vivo model using γ-H2AX immunofluorescence staining and confocal laser scanning microscopy (CLSM) to investigate its applicability in nuclear medicine dosimetry research. Liver and testis were selected as the organs to study after intravenous administration of 111InCl3. Results: In this study, we developed and validated a method that combines ex vivo γ-H2AX foci labeling of tissue sections with in vivo systemically irradiated mouse testis and liver tissues. The method includes CLSM imaging for intracellular cell-specific γ-H2AX foci detection and quantification and absorbed dose calculations. After exposure to ionizing radiation from 111InCl3, both hepatocytes and non-hepatocytes within the liver showed an absorbed dose-dependent elevation of γ-H2AX foci, whereas no such correlation was seen for the testis tissue. Conclusion: It is possible to detect and quantify the radiation-induced γ-H2AX foci within the tissues of organs at risk after internal irradiation. We conclude that our method developed is an appropriate tool to study dose–response relationships in animal organs and human tissue biopsies after internal exposure to radiation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- NATURVETENSKAP -- Fysik -- Annan fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Other Physics Topics (hsv//eng)
Keyword
- In
- Absorbed dose
- DNA damage
- Internal irradiation
- Liver
- Testis
- Tissue level
- γ-H2AX
Publication and Content Type
- art (subject category)
- ref (subject category)
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