Endogenous and exogenous sources cause oxidatively induced DNA damage in living organisms by a variety of mechanisms. The resulting DNA lesions are mutagenic and, unless repaired, lead to a variety of mutations and consequently to genetic instability, which is a hallmark of cancer. Oxidatively induced DNA damage is repaired in living cells by different pathways that involve a large number of proteins. Unrepaired and accumulated DNA lesions may lead to disease processes including carcinogenesis. Mutations also occur in DNA repair genes, destabilizing the DNA repair system. A majority of cancer cell lines have somatic mutations in their DNA repair genes. In addition, polymorphisms in these genes constitute a risk factor for cancer. In general, defects in DNA repair are associated with cancer. Numerous DNA repair enzymes exist that possess different, but sometimes overlapping substrate specificities for removal of oxidatively induced DNA lesions. In addition to the role of DNA repair in carcinogenesis, recent evidence suggests that some types of tumors possess increased DNA repair capacity that may lead to therapy resistance. DNA repair pathways are drug targets to develop DNA repair inhibitors to increase the efficacy of cancer therapy. Oxidatively induced DNA lesions and DNA repair proteins may serve as potential biomarkers for early detection, cancer risk assessment, prognosis and for monitoring therapy. Taken together, a large body of accumulated evidence suggests that oxidatively induced DNA damage and its repair are important factors in the development of human cancers. Thus this field deserves more research to contribute to the development of cancer biomarkers, DNA repair inhibitors and treatment approaches to better understand and fight cancer.
"The consequences of oxidative damage , genomic rearrangements , and strand breaks , are sensed by repair proteins ( Dizdaroglu , 2012 ) . For example , 8 - oxoG is excised by OGG1 a key component of the mitochondrial and nuclear base excision repair pathway ( Radak et al . "
[Show abstract][Hide abstract] ABSTRACT: Acute exercise increases reactive oxygen and nitrogen species generation. This
phenomenon is associated with two major outcomes: (1) redox signaling and (2)
macromolecule damage. Mechanistic knowledge of how exercise-induced redox
signaling and macromolecule damage are interlinked is limited. This review focuses
on the interplay between exercise-induced redox signaling and DNA damage, using
hydroxyl radical (·OH) and hydrogen peroxide (H2O2) as exemplars. It is postulated that
the biological fate of H2O2 links the two processes and thus represents a bifurcation
point between redox signaling and damage. Indeed, H2O2 can participate in two electron
signaling reactions but its diffusion and chemical properties permit DNA oxidation
following reaction with transition metals and ·OH generation. It is also considered that
the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox
signaling mechanism. Further layers of interaction are provided by the redox regulation
of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall,
exercise-induced redox signaling and DNA damage may be interlinked to a greater extent
than was previously thought but this requires further investigation.
Frontiers in Physiology 06/2015; 6. DOI:10.3389/fphys.2015.00182/abstract · 3.53 Impact Factor
"The oxidized guanine (8-oxodG) has great biological importance as this is a mutagenic lesion that induces G-T transversions. It may also impair DNA replication and transcription and may be an intermediate for other types of lesions in DNA  . Substantial evidence suggests that mitochondrial DNA may be more vulnerable than nuclear DNA to certain kinds of damage, in particular, ROS-mediated lesions   . "
[Show abstract][Hide abstract] ABSTRACT: The increased production of reactive oxygen species (ROS) plays a key role in pathogenesis of diabetic complications. ROS are generated by exogenous and endogenous factors such as during hyperglycemia. When ROS production exceeds the detoxification and scavenging capacity of the cell, oxidative stress ensues. Oxidative stress induces DNA damage and when DNA damage exceeds the cellular capacity to repair it, the accumulation of errors can overwhelm the cell resulting in cell death or fixation of genome mutations that can be transmitted to future cell generations. These mutations can lead to and/or play a role in cancer development. This review aims at (i) understanding the types and consequences of DNA damage during hyperglycemic pregnancy; (ii) identifying the biological role of DNA repair during pregnancy, and (iii) proposing clinical interventions to maintain genome integrity. While hyperglycemia can damage the maternal genetic material, the impact of hyperglycemia on fetal cells is still unclear. DNA repair mechanisms may be important to prevent the deleterious effects of hyperglycemia both in mother and in fetus DNA and, as such, prevent the development of diseases in adulthood. Hence, in clinical practice, maternal glycemic control may represent an important point of intervention to prevent the deleterious effects of maternal hyperglycemia to DNA.
BioMed Research International 08/2014; 2014:676758. DOI:10.1155/2014/676758 · 3.17 Impact Factor
"Current findings indicate both a trigger role of the oxidatively generated DNA damage in cell malignancy and their accumulation in tumors. Therefore, the impairment of the catalytic function of the OGG1 DNA glycosylase is assumed to affect susceptibility to cancer as well as to other oxidative pathologies (Dizdaroglu, 2012; Simonelli et al., 2013). Functional studies reveal the impact of certain polymorphic variants of the XRCC1 gene on the cellular genotoxic response and BER efficiency (Abdel- Rahman & El-Zein, 2000; Takanami et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: Abstract Context: The study of DNA base and nucleotide excision repair gene polymorphisms in bladder cancer seems to have a predictive value because of the evident relationship between the DNA damage response induced by environmental mutagens and cancer predisposition. Objective: The objective was to determine OGG1 Ser326Cys, XRCC1 Arg399Gln, XPD Asp312Asn, and ERCC6 Met1097Val polymorphisms in bladder cancer patients as compared to controls. Methods: Both groups were predominantly represented by Belarusians and Eastern Slavs. DNA samples from 336 patients and 370 controls were genotyped using a PCR-RFLP method. Results: The genotype distributions were in agreement with the Hardy-Weinberg equilibrium. The minor allele frequencies in the control population were in the range of those in Caucasians in contrast to Asians. The OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes were inversely associated with cancer risk (OR [95% CI] = 0.69 [0.50-0.95] and 1.35 [1.0-1.82], respectively). The contrasting effects of these genotypes were potentiated due to their interactions with smoking habit or age. Conclusions: Among four DNA repair gene polymorphisms, the OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes might be recognized as potential genetic markers modifying susceptibility to bladder cancer in Belarus.
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