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.
Highlights
Many decades of experimental research in cellular and molecular radiation biology have provided evidence suggesting that DNA damage plays a critical role in a plethora of human pathologies, including cancer, premature aging and chronic inflammatory conditions [1]
Apart from these environmental agents and genotoxic chemicals, DNA aberrations can arise from physiological processes such as base mismatches introduced during DNA replication [7] and from the release of reactive oxygen and nitrogen species (ROS/RNS) upon oxidative respiration or through redox-cycling events mediated by heavy metals [8]
The results showed an elevation of double strand breaks (DSBs) manifested as γH2AX foci in PBL, representing normal tissues in the irradiated thorax volume, 1 hour after fraction one and γH2AX foci numbers returned to near baseline values in 24 hours after treatment
Summary
Many decades of experimental research in cellular and molecular radiation biology have provided evidence suggesting that DNA damage plays a critical role in a plethora of human pathologies, including cancer, premature aging and chronic inflammatory conditions [1]. Our knowledge of the mechanistic basis of the strong link between IR and carcinogenesis has been based on early studies using various animal models and it is concluded that radiation tumorigenesis proceeds in a conventional multi-step mode following radiation-induced key gene losses from single-target cells (including possible stem cells) [15] These genes can be DNA damage response, apoptotic and cell cycle control genes and others. They suggest that these chromosomal abnormalities originate from the repair of radiation-induced DNA damage. There is a great need for improved detection techniques at cellular and tissue level that will provide valuable information for understanding the cellular mechanisms to process clustered DNA lesions [29]
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