Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis
Ifigeneia V. Mavragani 1, Zacharenia Nikitaki 1
, Maria P. Souli 1, Asef Aziz 2, Somaira Nowsheen 3,4, Khaled Aziz 3, Emmy Rogakou 5 and Alexandros G. Georgakilas 1,*
, Maria P. Souli 1, Asef Aziz 2, Somaira Nowsheen 3,4, Khaled Aziz 3, Emmy Rogakou 5 and Alexandros G. Georgakilas 1,*
1
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece
2
Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA
3
Mayo Medical Scientist Training Program, Mayo Medical School and Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA
4
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA
5
First Department of Pediatrics, “Aghia Sophia” Children’s Hospital, Medical School, University of Athens, 11527 Athens, Greece
*
Author to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Cancers 2017, 9(7), 91; https://doi.org/10.3390/cancers9070091
Received: 26 May 2017 / Revised: 6 July 2017 / Accepted: 14 July 2017 / Published: 18 July 2017
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
Abstract
Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair. View Full-TextKeywords:
ionizing radiation effects; DNA damage and repair; complex DNA damage; carcinogenesis; immune response; radiation therapy
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Mavragani, I.V.; Nikitaki, Z.; Souli, M.P.; Aziz, A.; Nowsheen, S.; Aziz, K.; Rogakou, E.; Georgakilas, A.G. Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis. Cancers 2017, 9, 91.
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