DNA base excision repair as a biomarker in molecular epidemiology studies

Collins, Andrew; Gaivão, Isabel

doi:10.1016/j.mam.2007.05.005

Cited by 55 publications

(38 citation statements)

References 44 publications

(49 reference statements)

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“…This could explain the reported interindividual variability in OGG1 activity (18,37) and the lack of a good correlation between OGG1 mRNA levels and DNA glycosylase activity found in population based studies (37). Age-associated loss of 8-oxoG DNA glycosylase activity (19,38) or accumulation of 8-oxoG in DNA (39) might also reflect increased in oxidative stress over the life span of a tissue. In addition, this sensitivity may explain some of the variability in the results of association studies on the OGG1-326 genotype and cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Oxidation Status of Human OGG1-S326C Polymorphic Variant Determines Cellular DNA Repair Capacity

et al. 2009

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The hOGG1 gene encodes the DNA glycosylase that removes the mutagenic lesion 7,8-dihyro-8-oxoguanine (8-oxoG) from DNA. A frequently found polymorphism resulting in a serine to cysteine substitution at position 326 of the OGG1 protein has been associated in several molecular epidemiologic studies with cancer development. To investigate whether the variant allele encodes a protein with altered OGG1 function, we compared the 8-oxoG repair activity, both in vivo and in cell extracts, of lymphoblastoid cell lines established from individuals carrying either Ser/Ser or Cys/Cys genotypes. We show that cells homozygous for the Cys variant display increased genetic instability and reduced in vivo 8-oxoG repair rates. Consistently, their extracts have an almost 2-fold lower basal 8-oxoG DNA glycosylase activity when compared with the Ser variant. Treatment with reducing agents of either the Cys variant cells directly or of protein extracts from these cells increases the repair capacity to the level of the Ser variant, whereas it does not affect the activity in cells or extracts from the latter. Furthermore, the DNA glycosylase activity of cells carrying the Cys/Cys alleles is more sensitive to inactivation by oxidizing agents when compared with that of the Ser/Ser cells. Analysis of the redox status of the OGG1 protein in the cells confirms that the lower activity of OGG1-Cys326 is associated with the oxidation of Cys326 to form a disulfide bond. Our findings support the idea that individuals homozygous for the OGG1-Cys variant could more readily accumulate mutations under conditions of oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Oxidation Status of Human OGG1-S326C Polymorphic Variant Determines Cellular DNA Repair Capacity

et al. 2009

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“…It is likely that aerobic fitness is related to higher antioxidant capacity, reduced DNA damage, or with increased DNA repair capacity, which would favor a lower nuclear DNA damage. In fact, it seems reasonable to suppose that a higher repair rate will lead to a decrease in the level of damage and considering the oxidative stress mechanisms, the more ROS is produced, the more repair should be induced, and consequently, the level of damage might be kept constant (Collins and Gaivao 2007). Concerning the role of physical exercise in the DNA repair mechanisms, very little has yet been studied.…”

Section: Introductionmentioning

confidence: 99%

“…Concerning the role of physical exercise in the DNA repair mechanisms, very little has yet been studied. Considering that chronic exercise increases antioxidant capacity, it seems likely to expect a reduction of DNA damage resulting from increase in both repair and antioxidant capacity (Collins and Gaivao 2007).…”

Section: Introductionmentioning

confidence: 99%

Effects of combined physical exercise training on DNA damage and repair capacity: role of oxidative stress changes

Soares

Silva

Oliveira

et al. 2015

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Regular physical exercise has been shown to be one of the most important lifestyle influences on improving functional performance, decreasing morbidity and all causes of mortality among older people. However, it is known that acute physical exercise may induce an increase in oxidative stress and oxidative damage in several structures, including DNA. Considering this, the purpose of this study was to identify the effects of 16 weeks of combined physical exercise in DNA damage and repair capacity in lymphocytes. In addition, we aimed to investigate the role of oxidative stress involved in those changes. Fifty-seven healthy men (40 to 74 years) were enrolled in this study. The sample was divided into two groups: the experimental group (EG), composed of 31 individuals, submitted to 16 weeks of combined physical exercise training; and the control group (CG), composed of 26 individuals, who did not undergo any specifically orientated physical activity. We observed an improvement of overall physical performance in the EG, after the physical exercise training. A significant decrease in DNA strand breaks and FPG-sensitive sites was found after the physical exercise training, with no significant changes in 8-oxoguanine DNA glycosylase enzyme activity. An increase was observed in antioxidant activity, and a decrease was found in lipid peroxidation levels after physical exercise training. These results suggest that physical exercise training induces protective effects against DNA damage in lymphocytes possibly related to the increase in antioxidant capacity.

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“…An investigation of expression profiles of some BER and NER genes in tumor tissue did provide preliminary characterizations (16). Previous studies carried out on peripheral blood mononuclear cells (PBMC) showed suppressed BER and NER capacities in patients with CRC compared with healthy individuals (17)(18)(19). However, the validity of blood as a surrogate for cancer tissue to estimate DNA repair capacity (DRC) remains disputable.…”

Section: Introductionmentioning

confidence: 99%

Functional, Genetic, and Epigenetic Aspects of Base and Nucleotide Excision Repair in Colorectal Carcinomas

Slyšková

Korenkova

Collins

et al. 2012

Clinical Cancer Research

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Purpose: DNA repair capacity (DRC) is a determinant not only of cancer development but also of individual response to therapy. Previously, altered base and nucleotide excision repair (BER and NER) have been described in lymphocytes of patients with sporadic colorectal cancer. We, for the first time, evaluate both excision repair capacities in human colon biopsies to study their participation in colorectal tumorigenesis.Experimental design: Seventy pairs of tumor and adjacent healthy tissues were analyzed for BER-and NER-specific DRC by a comet repair assay. Tissue pairs were further compared for expression levels of a panel of 25 BER and NER genes complemented by their promoter methylation status.

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DNA base excision repair as a biomarker in molecular epidemiology studies

Cited by 55 publications

References 44 publications

Oxidation Status of Human OGG1-S326C Polymorphic Variant Determines Cellular DNA Repair Capacity

Oxidation Status of Human OGG1-S326C Polymorphic Variant Determines Cellular DNA Repair Capacity

Effects of combined physical exercise training on DNA damage and repair capacity: role of oxidative stress changes

Functional, Genetic, and Epigenetic Aspects of Base and Nucleotide Excision Repair in Colorectal Carcinomas

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