Stress-induced DNA damage biomarkers: applications and limitations

Abstract

A variety of environmental stresses like chemicals, UV and ionizing radiation and organism's endogenous processes such as replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damage plays a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g., X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e., single, complex DNA lesions etc. that can be used as DNA damage biomarkers. We critically compare DNA damage detection methods and their limitations. In addition, we suggest the use of DNA repair gene products as biomarkes for identification of different types of stresses i.e., radiation, oxidative, or replication stress, based on bioinformatic approaches and meta-analysis of literature data.

Comet Assay Assessment of DNA Damage in Buccal Mucosa Cells Exposed to X-Rays via Panoramic Radiography

“…In other words, all radiation doses are considered harmful. 5 The effects of panoramic radiography have been widely studied, 1,6,7 leading to the findings that panoramic radiography causes chromosomal damage, nuclear changes, and cell death. However, no previous reports have addressed the DNA-damaging effects of radiation from panoramic radiography in buccal mucosa cells.…”

“…6 This assay, which is sensitive enough to measure injuries to single or multiple DNA strands, is an excellent method for monitoring the biological processes associated with DNA damage. 8 Although human studies of DNA damage have largely used lymphocytes, these cells are difficult to harvest, and the process is invasive and may cause discomfort to patients.…”

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

“…When LET (Linear Energy Transfer) increases the complexity (number of individual lesions in one multiple damage site) increases, since more ionization events take place in a defined volume. In a close collaboration with Iliakis' (Germany), Ravanat's (France), and Martin's (Australia) groups, the DNA Damage Laboratory of A. Georgakilas (NTUA, Greece) has proposed an improvement of methodologies used for the detection of oxidative clustered DNA lesions in vitro and in vivo with special emphasis on the in situ detection including bystander effects [62][63][64][65]. In addition, bioinformatics has been used to better understand the DNA damage response mechanisms relating to ionizing radiationinduced DNA damage and their association with inflammatory and immune response pathways [66][67][68][69][70][71].…”

Role of Flavonoids in DNA Damage and Carcinogenesis Prevention

“…Two different types of strategies categorized as direct and indirect methods are used to measure radiation-induced DNA damage [7]. The most commonly used indirect methods to visualize the DNA damaging protective effects of flavonoids are micronuclei formation and comet assay, which can measure biological consequences of DNA damage.…”