Disease relevance of Ogg1

• Here, we demonstrate that deficiencies in Myh and Ogg1 predispose 65.7% of mice to tumors, predominantly lung and ovarian tumors, and lymphomas [1].
• We found that lung adenoma/carcinoma spontaneously developed in Ogg1 knockout mice approximately 1.5 years after birth in which 8-oxoG was found to accumulate in their genomes [2].
• The rate of developing malignant tumors in Ogg1 knockout mice was also significantly higher (88.5%; squamous cell carcinomas, 73.1%; sarcomas, 15.4%) than in wild-type mice (50.0%; squamous cell carcinomas, 41.7%; sarcomas, 8.3%) [3].
• Results: Inflammatory lesions induced in the gastric mucosa of H. pylori-infected mice, corresponding to a moderate gastritis, were less severe in Ogg1(-/-) than in Wt Big Blue mice [4].
• During the course of study the mice appeared normal, although a decrease of body weight gain in both Ogg1(-/-) and Ogg1(+/+) mice exposed to KBrO3, and some kidney malfunction in KBrO3 treated Ogg1(-/-) mice was observed [5].

High impact information on Ogg1

• Csb(-/-) mice crossed with a strain defective in base excision repair (Ogg1) demonstrated no enhanced neurodegenerative phenotype [6].
• Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice [7].
• Expression of the mouse Ogg1 protein in the homozygous ogg1(-/-) cell line restored the ability to remove 8-OxoG in the NTS [8].
• To assess the role of the Ogg1 DNA glycosylase in the transcription-coupled repair (TCR) of the mutagenic lesion, 7, 8-dihydro-8oxoguanine (8-OxoG), we have investigated the removal of this lesion in wild-type and ogg1(-/-) null mouse embryo fibroblast (MEF) cell lines [8].
• Ogg1 mRNA is expressed in several mouse tissues; highest levels were detected in testes [9].

Biological context of Ogg1

• However, no remarkable up-regulation of Ogg1-an oxidative DNA damage repair gene-was observed in the tumor areas, but the expression of Trail-an apoptosis-signaling ligand gene-was significantly down-regulated in the tumor tissues [10].
• Combined, these observations suggest that a cooperative function between Ogg1 and Mutyh exists to prevent 8-oxoG-related mutagenesis in mammals [11].
• Cell proliferation in liver of Mmh/Ogg1-deficient mice enhances mutation frequency because of the presence of 8-hydroxyguanine in DNA [12].
• We have analysed the steady-state levels and repair kinetics of oxidative DNA modifications in cells of homozygous ogg1(-/-) null mice, which are deficient in Ogg1 protein, a DNA repair glycosylase that removes the miscoding base 8-hydroxyguanine (8-oxoG) from the genome [13].
• The Ogg1 gene is localized to the mouse chromosome 6E [14].

Anatomical context of Ogg1

• Furthermore, Ogg1 was not up-regulated in murine B cells from germinal centers [15].
• The expression and activity of 8-oxoguanosine DNA-glycosylase (Ogg1), a key enzyme responsible forthe clearance of the oxidized DNA base 8-hydroxy-2'-deoxyguanosine (oxo8dG), was determined in the cerebellum (CB) and the caudate and the putamen (CP) of male Balb/c, ICR, and C57BL/J mice [16].
• In these conditions, the H. pylori-SS1 infection in the Ogg1(-/-) mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months [4].
• 8-Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate treatment in kidney but not thyroid [17].
• Surprisingly, when Ogg1(-/-) and Ogg1(+/+) mice were sacrificed at 52 weeks, no tumor formation could be found in kidney or other organs such as lung, liver, spleen, thymus, stomach and intestine [5].

Associations of Ogg1 with chemical compounds

• Accumulation of the oxidative base lesion 8-hydroxyguanine in DNA of tumor-prone mice defective in both the Myh and Ogg1 DNA glycosylases [18].
• 8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis [3].
• Oxidative purine modifications including 8-oxoG were quantified by means of an alkaline elution assay in combination with Fpg protein, the bacterial functional analogue of Ogg1 protein [13].
• The mouse Ogg1 protein acts efficiently on duplexes in which the 8-OH-Gua is paired with a cytosine but is inactive on 8-OH-Gua: Ade pair, consistently with its proposed biological role in the avoidance of mutations [14].
• The Mth1 mRNA level decreased soon after kainate administration and then quickly recovered beyond the basal level, and a continuously increased MTH1 protein level was observed, whereas the Ogg1 mRNA level remained constant [19].

Other interactions of Ogg1

• Functional cooperation of Ogg1 and Mutyh in preventing G: C-->T: a transversions in mice [11].
• Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption [2].

Analytical, diagnostic and therapeutic context of Ogg1

• Partial hepatectomy was performed on Ogg1(+/-) and Ogg1(-/-) mice after being treated with KBrO(3) for 12 weeks [12].
• Western blot analysis and repair activity in extracts from Ogg1(-/-) mice revealed that OGG1 was responsible for the efficient 8-oxoG removal from prenatal mice [20].
• We studied oxidative damage to DNA in broncho-alveolar lavage cells, lungs, and liver after 4 x 1.5 h inhalations of DEP (20 mg/m3) in Ogg1-/- and wild type (WT) mice with similar extent of inflammation [21].

References