Radiation-Induced DNA Damage: Formation, Measurement, and Biochemical Features

Abstract

Most of the reactions induced by *OH radicals (indirect effects) and by one-electron oxidation (direct effects) as the result of exposure to ionizing radiation may be described for the four main DNA nucleobases. Relevant information is now available on the formation of single and tandem base lesions implicating guanine as the most susceptible DNA component to the deleterious effects of ionizing radiation. In contrast, there is still a paucity of information on the radiation-induced formation of base damage within cellular DNA. This is mostly a result of difficulties associated with the measurement of oxidized purine and pyrimidine bases that appear to be generated in very low yields. This is illustrated by the measurement of low amounts of E. coli formamidopyrimidine glycosylase- and endonuclease-III-sensitive sites in the DNA of neoplastic monocytes upon exposure to gamma rays (48 and 53 per 10(9) bases and per Gy, respectively) using a modified comet assay (the overall number of strand breaks and alkali-labile sites was estimated to be 130 per 10(9) bases and per Gy). More specifically, the level of several radiation-induced modified bases, including thymine glycols, 5-formyluracil, 5-(hydroxymethyl)uracil, 8-oxo-7,8-dihydroguanine, and 8-oxo-7,8-dihydroadenine, together with related formamidopyrimidine derivatives was assessed using the suitable HPLC-MS/MS method. Information is also provided on the substrate specificity of DNA repair enzymes and the mutagenic potential of base lesions using site-specific modified oligonucleotides as the probes.

The biochemical changes in rats blood serum levels exposed to different gamma radiation doses

“…In actively metabolizing cells, there is considerable water apart from the target macromolecules. These ROS can induce oxidative damage to vital cellular molecules and structures including DNA, lipids, proteins, and membranes (Cadet et al, 2004). Lipid peroxidation such as malondialdehyde (MDA) and 4-hydroxynonenal (4NHE) have the ability to interact with and alter macromolecules, possibly resulting in diseases (Petersen and Doorn, 2004).…”

Anti-inflammatory effects of ozonated water in an experimental mouse model

“…Oxidative damage to vital cellular molecules and structures such as DNA, lipids, proteins and membranes is induced by ROS (23). The mitochondrial electron transport chain is a major source of intracellular ROS and is susceptible to damage initiated by ROS (24).…”

Mentha piperita as a pivotal neuro-protective agent against gamma irradiation induced DNA fragmentation and apoptosis

“…Oxidative stress might subsequently increase the frequency of transformation of cells to a malignant phenotype leading to apoptosis (Gorbunov et al 2000). Ionizing radiation exerted its deleterious effect by interacting with water in cells and producing hydrogen peroxide and hydroxyl radicals abstracting hydrogen atom from sugar residues, causing base release and strand break of DNA or RNA producing impaired gene transcription (Cadet et al 2004;Wang et al 2010). Moreover, interaction of H 2 O 2 with Fe2 ?…”