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Predictive Biomarkers in Personalized Laboratory Diagnoses and Best Practices Outcome Monitoring for Musculoskeletal Health
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
Oxidative stress describes the injury caused to cells resulting from increased formation of free radicals and/or decreased antioxidant reserve. Oxidative stress can define bone cell behavior [58] and is seen to play a crucial role in the development of conditions like osteopenia [59], diabetes, and cardiovascular disease. Testing for 8-oxoguanine provides important information about oxidative stress and its effects on DNA and the genetic sequence. The test is well validated as a measure of nuclear and mitochondrial DNA oxidative stress and is well supported in the research literature [60].
Introducing Molecular Biology of Head and Neck Cancer
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Nikolina Vlatković, Mark T. Boyd
Probably the most significant mutagenic events are those caused by environmental carcinogens, because they affect the most patients and result in cancers with poorer outcomes. The two primary sources of these carcinogens for head and neck cancers are tobacco smoke and alcohol. A critical feature of carcinogenic chemicals is that they often produce chemical modifications, typically of the nucleic acid bases, for which no specific repair pathway exists. This is hardly surprising since the variety of different chemical adducts that smoking alone can cause may exceed one hundred (tobacco smoke contains approximately 50–60 carcinogenic compounds that may display multiple effects on the DNA).33–35 In contrast, the oxidation of one of the DNA bases, guanine, to 8-oxo-guanine by the endogenous production of ROS—one of the most common chemical modifications of DNA to occur—can be repaired by base excision repair (BER) mechanisms initiated by an enzyme that specifically recognizes this common lesion: 8-oxoguanine glycosylase (OGG1).36–38
Complications of External-Beam Radiation Therapy
Published in Kevin R. Loughlin, Complications of Urologic Surgery and Practice, 2007
The pathophysiology of radiation effect on the bladder and urethra is not well studied. Presumably, the same types of changes that one sees with rectal biopsy would also be seen in the bladder during or after radiation in patients with symptoms (67). These would be changes such as fibrosis, progressive endarteritis, thinning of the bladder mucosa and muscular tissues, and inflammation of telangiectasia. The cellular effect of radiation on the normal bladder epithelium is not known, except for some evidence from the Academy of Medical Sciences of Ukraine in Kiev (68). Two hundred and four patients with chronic cystitis after the Chernobyl accident underwent bladder biopsies with immunohistochemical studies. Chemical evidence of oxidative stress generated by the ionizing radiation was present as evidenced by elevated levels of 8-hydroxy-2-deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic endonuclease, and xerodermapigmentosum A endonuclease. While these findings are not strictly applicable to patients undergoing therapeutic radiation, there are likely to be similarities. One major difference is, of course, that the Ukrainian patients had chronic exposure over years, which probably overwhelmed their DNA-damage repair.
Molecular radiobiology and the origins of the base excision repair pathway: an historical perspective
Published in International Journal of Radiation Biology, 2023
However, in the cell, all of the enzymes required to repair the damages in a cluster are present. Thus, it is possible that the two damage-containing strands could be sequentially repaired. To address this question, Lynn Harrison, a postdoc in our laboratory, reconstituted the entire base excision repair system using a bistranded substrate containing 8-oxoguanine closely opposed to a single strand break (Harrison et al. 1999) (Figure 3). This assay included a DNA glycosylase that recognized 8-oxoG, an AP endonuclease, a DNA polymerase and DNA ligase. If the 8-oxoG was one nucleotide away from the single strand break, the strand break was repaired. However, if the 8-oxoG was three nucleotides away from the single strand break, it could now be cleaved by the DNA glycosylase resulting in a double strand break. This same result was obtained with a number of base lesions (Blaisdell et al. 2001).
Consequences and repair of radiation-induced DNA damage: fifty years of fun questions and answers
Published in International Journal of Radiation Biology, 2022
Several years later Zafer Hatahet, a post-doctoral associate, used in vitro selection to identify sequence contexts that enhanced the mutational potential of 8-oxoguanine (Hatahet et al. 1998). 8-oxoG is the most common oxidative lesion and is removed in E. coli by Fpg glycosylase. If the lesion is not removed prior to replication the replicative polymerase most often inserts an A opposite which is then removed by MutY and a C inserted. If the A is not removed, the mutation is fixed to a G-C to T-A transversion. Zafer engineered a pool of 48 52-mers containing 8-oxoG surrounded on both sides by 4 random nucleotides. This pool was converted to a duplex by T4 DNA polymerase and then exhaustively digested with Fpg glycosylase. The surviving sequences, products of poor Fpg repair and misinsertion of A by T4 polymerase (8-oxoG-A pairs are poor substrates for Fpg) were identified as mutagenic hotspots. Kinetic analysis showed that these combined effects led to a 102–103 increase in the mutagenic potential of 8-oxoG and correlated strongly with G-T transversion hotspots reported for E. coli lacI as well as human p53 and factor IX genes.
Mitochondrial DNA copy number, damage, repair and degradation in depressive disorder
Published in The World Journal of Biological Psychiatry, 2020
Piotr Czarny, Paulina Wigner, Justyna Strycharz, Ewa Swiderska, Ewelina Synowiec, Magdalena Szatkowska, Agnieszka Sliwinska, Monika Talarowska, Janusz Szemraj, Kuan-Pin Su, Michael Maes, Tomasz Sliwinski, Piotr Galecki
Major depressive disorder (MDD) is associated with multifactorial pathophysiology including inflammation (Dowlati et al. 2010; Pasco et al. 2010; Leonard and Maes 2012; Su 2012) and nitrosative and oxidative stress (Pasco et al. 2010; Gardner and Boles 2011; Alcocer-Gómez et al. 2014; Anderson and Maes 2014; Satyanarayanan et al. 2018; Wigner et al. 2018). In depressed patients, oxidative stress is manifested by the presence of elevated lipid peroxidation and production of mitochondrial reactive oxygen species (mtROS), as well as increased concentrations of 8-oxoguanine (8-oxoG), a marker of oxidative DNA damage (Irie et al. 2001; Irie et al. 2003; Forlenza and Miller 2006; Kupper et al. 2009; Maes et al. 2009a; Wei et al. 2009; Alcocer-Gómez et al. 2014; Anderson and Maes 2014; Lindqvist et al. 2017). However, while meta-analysis revealed oxidative stress-associated elevation of 8-oxoG and F2-isoprostanes in depression (Black et al. 2015), a study on a large cohort of adults indicated no change in 8-oxoG level (Black et al. 2017).