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Title: DNA Double-Strand Break Rejoining in Complex Normal Tissues

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 {gamma}H2AX 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 {gamma}H2AX 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 {gamma}H2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for {gamma}H2AX foci loss, despite their clearly different clinical radiation responses. Conclusion: The identical kinetics of DSB rejoining measuredmore » 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.« less
Authors:
 [1] ;  [2] ;  [3] ; ;  [2] ; ;  [4] ;  [2]
  1. Department of Radiation Oncology, Saarland University, Homburg/Saar, Saarland (Germany), E-mail: claudia.ruebe@uks.eu
  2. Department of Radiation Oncology, Saarland University, Homburg/Saar, Saarland (Germany)
  3. (China)
  4. Institute for Molecular Cell Biology, Saarland University, Homburg/Saar, Saarland (Germany)
Publication Date:
OSTI Identifier:
21172473
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 72; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2008.07.017; PII: S0360-3016(08)03042-3; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; BRAIN; DNA; DNA REPAIR; HEART; HOMEOSTASIS; IN VIVO; IONIZING RADIATIONS; KIDNEYS; LUNGS; MICE; RADIATION DOSES; RADIONUCLIDE KINETICS; RADIOSENSITIVITY; SMALL INTESTINE; STRAND BREAKS; WHOLE-BODY IRRADIATION