Journal
RADIATION PHYSICS AND CHEMISTRY
Volume 128, Issue -, Pages 26-35Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.radphyschem.2016.06.020
Keywords
Non-DSB clustered DNA lesions; Ionizing radiation; Damage simulations; DNA repair; Fluorescence microscopy; Colocalization assays
Funding
- EU Marie Curie Reintegration Grant [MC-CIG-303514]
- COST Action 'Biomimetic Radical Chemistry' [CM1201]
- NASA Space Radiation Risk Assessment Project (NASA) [NAS9-02078]
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Ionizing radiation results in various kinds of DNA lesions such as double strand breaks (DSBs) and other non-DSB base lesions. These lesions may be formed in close proximity (i.e., within a few nanometers) resulting in clustered types of DNA lesions. These damage clusters are considered the fingerprint of ionizing radiation, notably charged particles of high linear energy transfer (LET). Accumulating theoretical and experimental evidence suggests that the induction of these clustered lesions appears under various irradiation conditions but also as a result of high levels of oxidative stress. The biological significance of these clustered DNA lesions pertains to the inability of cells to process them efficiently compared to isolated DNA lesions. The results in the case of unsuccessful or erroneous repair can vary from mutations up to chromosomal instability. In this mini review, we discuss of several Monte Carlo simulations codes and experimental evidence regarding the induction and repair of radiation-induced non-DSB complex DNA lesions. We also critically present the most widely used methodologies (i.e., gel electrophoresis and fluorescence microscopy [in situ colocalization assays]). Based on the comparison of different approaches, we provide examples and suggestions for the improved detection of these lesions in situ. Based on the current status of knowledge, we conclude that there is a great need for improvement of the detection techniques at the cellular or tissue level, which will provide valuable information for understanding the mechanisms used by the cell to process clustered DNA lesions. (C) 2016 Elsevier Ltd. All rights reserved.
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