Development of an enzymatic DNA repair assay for molecular epidemiology studies: Distribution of OGG activity in healthy individuals

Paz-Elizur, Tamar; Elinger, Dalia; Leitner‐Dagan, Yael; Blumenstein, Sara; Krupsky, Meir; Berrébi, Alain; Schechtman, Edna; Livneh, Zvi

doi:10.1016/j.dnarep.2006.08.003

Cited by 100 publications

(86 citation statements)

References 41 publications

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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.…”

Section: Discussionmentioning

confidence: 93%

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: 93%

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

et al. 2009

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“…Studies on hepatic mitochondrial DNA have shown the levels of 8-oxo-dG to be 4-fold higher in the males compared with the females (36). Interestingly, studies by Paz-Elizur et al (37) showed a lack of gender differences in OGG1 (8-oxoguanine DNA glycosylase) activity, the enzyme responsible for removing 8-oxo-dG lesions from the DNA. Semiquantitative reverse transcription-PCR analysis of OGG1 mRNA expression in the skin from the unirradiated and acute UVB-exposed skin in this study showed no significant gender difference (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Gender Differences in UVB-Induced Skin Carcinogenesis, Inflammation, and DNA Damage

Thomas‐Ahner¹,

Wulff²,

Tober³

et al. 2007

Cancer Research

135

136

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The American Cancer Society reports the incidence of squamous cell carcinoma in males to be thrice the incidence in females. This increased squamous cell carcinoma incidence has been attributed to men accumulating more sun exposure and using less sun protection than women. To date, there have been no controlled studies examining the effect of gender on skin tumor development following equal doses of UVB. Gender differences in UVB-induced skin carcinogenesis were examined using the Skh-1 mouse model. After chronic exposure to equal doses of UVB, male mice developed tumors earlier and had more tumors than female mice; tumors in male mice tended to be larger, and the total tumor burden was greater than in females. In addition, tumors in males were of more advanced histologic grade compared with those of female mice. To evaluate the contribution of differences in inflammation and DNA damage to differences in skin carcinogenesis, male and female Skh-1 mice were exposed once to 2,240 J/m 2 UVB and examined 48 h after exposure. Surprisingly, male mice developed less of an inflammatory response, as determined by skin fold thickness and myeloperoxidase activity, compared with females. Interestingly, male mice showed more cutaneous oxidative DNA damage than the females and lower antioxidant levels. These results show a gender bias in skin carcinogenesis and suggest that the gender difference in tumor development is more influenced by the extent of oxidative DNA damage and antioxidant capacities than by inflammatory response. [Cancer Res 2007;67(7):3468-74]

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“…To measure such interindividual variations in DNA repair, we (13)(14)(15)(16)(17)(18) and others (19)(20)(21) took the approach of measuring the enzymatic activity of specific DNA repair enzymes, using peripheral blood mononuclear cell (PBMC) as the reporter tissue. Our primary focus was on DNA repair enzymes that target oxidative DNA damage, which has been implicated as a major factor in carcinogenesis (22).…”

Section: Introductionmentioning

confidence: 99%

Low Integrated DNA Repair Score and Lung Cancer Risk

Sevilya

Leitner‐Dagan

Pinchev

et al. 2014

Cancer Prevention Research

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DNA repair is a prime mechanism for preventing DNA damage, mutation, and cancers. Adopting a functional approach, we examined the association with lung cancer risk of an integrated DNA repair score, measured by a panel of three enzymatic DNA repair activities in peripheral blood mononuclear cells. The panel included assays for AP endonuclease 1 (APE1), 8-oxoguanine DNA glycosylase (OGG1), and methylpurine DNA glycosylase (MPG), all of which repair oxidative DNA damage as part of the base excision repair pathways. A blinded population-based case-control study was conducted with 96 patients with lung cancer and 96 control subjects matched by gender, age (AE1 year), place of residence, and ethnic group (Jews/non-Jews). The three DNA repair activities were measured, and an integrated DNA repair OMA (OGG1, MPG, and APE1) score was calculated for each individual. Conditional logistic regression analysis revealed that individuals in the lowest tertile of the integrated DNA repair OMA score had an increased risk of lung cancer compared with the highest tertile, with OR ¼ 9.7; 95% confidence interval (CI), 3.1-29.8; P < 0.001, or OR ¼ 5.6; 95% CI, 2.1-15.1; P < 0.001 after cross-validation. These results suggest that pending validation, this DNA repair panel of risk factors may be useful for lung cancer risk assessment, assisting prevention and referral to early detection by technologies such as low-dose computed tomography scanning. Cancer Prev Res; 7(4); 398-406. Ó2013 AACR.

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Development of an enzymatic DNA repair assay for molecular epidemiology studies: Distribution of OGG activity in healthy individuals

Cited by 100 publications

References 41 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

Gender Differences in UVB-Induced Skin Carcinogenesis, Inflammation, and DNA Damage

Low Integrated DNA Repair Score and Lung Cancer Risk

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