Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive gammaH2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues.
Methods And Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating gammaH2AX foci in various organs representative of both early-responding (small intestine) and late-responding (lung, brain, heart, kidney) tissues.
Results: The linear dose correlation observed in all analyzed tissues indicated that gammaH2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for gammaH2AX foci loss, despite their clearly different clinical radiation responses.
Conclusion: The identical kinetics of DSB rejoining measured in different organs suggest that tissue-specific differences in radiation responses are independent of DSB rejoining. This finding emphasizes the fundamental role of DSB repair in maintaining genomic integrity, thereby contributing to cellular viability and functionality and, thus, tissue homeostasis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijrobp.2008.07.017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Missing the mark(ers): circulating endothelial cells and endothelial-derived extracellular vesicles are elevated in sickle cell disease plasma.
Front Immunol
December 2024
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, United States.
Sickle cell disease (SCD) is a devastating hemolytic disease, marked by recurring bouts of painful vaso-occlusion, leading to tissue damage from ischemia/reperfusion pathophysiology. Central to this process are oxidative stress, endothelial cell activation, inflammation, and vascular dysfunction. The endothelium exhibits a pro-inflammatory, pro-coagulant, and enhanced permeability phenotype.
View Article and Find Full Text PDFGeneration of effective and specific human TCRs against tumor/testis antigen NY-ESO-1 in mice with humanized T cell recognition system.
Front Immunol
December 2024
Molecular Immunology and Gene Therapy, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.
View Article and Find Full Text PDFA microenvironment-adaptive GelMA-ODex@RRHD hydrogel for responsive release of HS in promoted chronic diabetic wound repair.
Regen Biomater
November 2024
Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China.
Chronic diabetic wounds present significant treatment challenges due to their complex microenvironment, often leading to suboptimal healing outcomes. Hydrogen sulfide (HS), a crucial gaseous signaling molecule, has shown great potential in modulating inflammation, oxidative stress and extracellular matrix remodeling, which are essential for effective wound healing. However, conventional HS delivery systems lack the adaptability required to meet the dynamic demands of different healing stages, thereby limiting their therapeutic efficacy.
View Article and Find Full Text PDFPrevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK inhibitors.
Theranostics
January 2025
College of Pharmacy, Research Institute of Pharmaceutical Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea.
Radiotherapy is a widely employed technique for eradication of tumor using high-energy beams, and has been applied to approximately 50% of all solid tumor patients. However, its non-specific, cell-killing property leads to inevitable damage to surrounding normal tissues. Recent findings suggest that radiotherapy-induced tissue damage contributes to the formation of a pro-tumorigenic microenvironment.
View Article and Find Full Text PDFIntroduction Cardiorespiratory fitness (CRF) is a key health indicator for assessing optimal physical function and overall well-being. Exploring the early impact of body mass index (BMI) and anthropometric measures on CRF in non-obese individuals is essential for identifying risk factors and guiding preventive strategies to address weight-related health challenges. This study aims to investigate the impact of BMI and anthropometric measures on CRF, focusing on maximal oxygen uptake (VO2max) and metabolic equivalents (METs) in non-obese adult males.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!