UNASSIGNED: This study aimed to explore genetic variations associated with DNA repair mechanisms to enhance the management of both oral cancer (OC) and oral precancer (OPC).
UNASSIGNED: A cohort of 380 patients diagnosed with OC and OPC, comprising 220 males and 160 females, was analyzed. Participants were categorized based on their tobacco-chewing habits, with corresponding control groups established. Key genetic markers investigated for polymorphisms included OGG1, APE1, and XRCC1.
UNASSIGNED: The XRCC1 Arg280H variant demonstrated significant associations with the susceptibility to both OC and OPC across various models. Further analyses, incorporating factors such as tobacco and alcohol consumption, unveiled a correlation between the XRCC1 Arg194Trp variant and an elevated risk of developing head and neck cancer. Stratified analyses also revealed an increased risk of OC or OPC based on the specific site of the cancer.
UNASSIGNED: The study underscores the importance of XRCC1 polymorphisms, particularly XRCC1 Arg280H and XRCC1 Arg194Trp, within the genetic framework of OC and OPC. Understanding these genetic associations provides valuable insights for the potential development of targeted interventions aimed at individuals predisposed to these conditions.

UNASSIGNED: DNA damage can lead to carcinogenesis if replication proceeds without proper repair. This study focused on the purification of a novel quercetin derivative present in Terminalia chebula fruit and studied its protective role in hepatoma cells due to H2O2-DNA damage.
UNASSIGNED: The pure compound obtained from the silica gel column was subjected to structural characterization using spectroscopic techniques. MTT assay was employed to select a non-toxic concentration of the isolated compounds on HepG2 and Chang liver cells. The antigenotoxic property of the compound on HepG2 and Chang liver cells was carried out by alkaline comet assay. Analyses of expression levels of mRNA for two DNA repair enzymes, OGG1 and NEIL1, in HepG2 and Chang liver cells, were carried out using the RT-PCR method.
UNASSIGNED: The pure compound obtained from the fraction-5 of diethyl ether extract was identified as a novel quercetin derivative and named 7-(but-2-en-1-yloxy)-2-(4(but-2-en-1-yloxy)-3-hydroxyphenyl)-3- (hexa-2,4-dien-1-yloxy)-6-hydroxy-4H-chromen-4-one. This compound recorded modest toxicity at the highest concentration tested (percentage cell viability at 100 μg/mL was 64.71 ± 0.38 for HepG2 and 45.32 ± 0.07 for Chang liver cells). The compound has demonstrated noteworthy protection against H2O2-induced DNA damage in both cell lines. Analyses of mRNA expression levels for enzymes OGGI and NEIL1 enzymes in HepG2 and Chang liver cells asserted the protective role of the isolated compound against H2O2-induced DNA damage.
UNASSIGNED: The protective effect of a novel quercetin derivative isolated from T. chebula in the hepatoma cells is reported here for the first time.

OBJECTIVE: To identify mtDNA and OGG1 as potential biomarker candidates for mechanical asphyxia.
METHODS: The human tissues are divided into experimental group (hanging and strangulation) and control groups (hemorrhagic shock, brain injury group, and poisoning group). Detected the expression of OGG1 and integrity of mtDNA in cardiac tissue of each group. We used over-OGG1 vector and siRNA-OGG1 transfecting H9C2 cell line to observe the function of OGG1 in hypoxic cells.
RESULTS: 1. mtDNA integrity decreased in the mechanical asphyxia group, OGG1 expression increased in mechanical asphyxia groups. They can be biomarkers for mechanical asphyxia. 2. OGG1 increased first and decreased in hypoxia-induced H9C2 cells. OGG1 upregulated the TFAM, NRF1, and Bcl2 in hypoxia-induced H9C2. OGG1 downregulated cleaved-Caspase3 in hypoxia-induced H9C2 cells. 3. In the normoxia condition, NAC maintained mtDNA integrity and decreased the mitochondrial membrane potential and amount of ATP.
CONCLUSIONS: mtDNA integrity and OGG1 expression can be biomarkers for mechanical asphyxia. OGG1 can maintain mtDNA integrity and maintain the stability of the mitochondrial membrane.

BACKGROUND: 8-Oxoguanine DNA glycosylase (OGG1), a well-known DNA repair enzyme, has been demonstrated to promote lung fibrosis, while the specific regulatory mechanism of OGG1 during pulmonary fibrosis remains unclarified.
METHODS: A bleomycin (BLM)-induced mouse pulmonary fibrosis model was established, and TH5487 (the small molecule OGG1 inhibitor) and Mitochondrial division inhibitor 1 (Mdivi-1) were used for administration. Histopathological injury of the lung tissues was assessed. The profibrotic factors and oxidative stress-related factors were examined using the commercial kits. Western blot was used to examine protein expression and immunofluorescence analysis was conducted to assess macrophages polarization and autophagy. The conditional medium from M2 macrophages was harvested and added to HFL-1 cells for culture to simulate the immune microenvironment around fibroblasts during pulmonary fibrosis. Subsequently, the loss- and gain-of function experiments were conducted to further confirm the molecular mechanism of OGG1/PINK1.
RESULTS: In BLM-induced pulmonary fibrosis, OGG1 was upregulated while PINK1/Parkin was downregulated. Macrophages were activated and polarized to M2 phenotype. TH5487 administration effectively mitigated pulmonary fibrosis, M2 macrophage polarization, oxidative stress and mitochondrial dysfunction while promoted PINK1/Parkin-mediated mitophagy in lung tissues of BLM-induced mice, which was partly hindered by Mdivi-1. PINK1 overexpression restricted M2 macrophages-induced oxidative stress, mitochondrial dysfunction and mitophagy inactivation in lung fibroblast cells, and OGG1 knockdown could promote PINK1/Parkin expression and alleviate M2 macrophages-induced mitochondrial dysfunction in HFL-1 cells.
CONCLUSIONS: OGG1 inhibition protects against pulmonary fibrosis, which is partly via activating PINK1/Parkin-mediated mitophagy and retarding M2 macrophage polarization, providing a therapeutic target for pulmonary fibrosis.

Cervical cancer cells possess high levels of reactive oxygen species (ROS); thus, increasing oxidative stress above the toxicity threshold to induce cell death is a promising chemotherapeutic strategy. However, the underlying mechanisms of cell death are elusive, and efficacy and toxicity issues remain. Within DNA, 8-oxo-7,8-dihydroguanine (8-oxoG) is the most frequent base lesion repaired by 8-oxoguanine glycosylase 1 (OGG1)-initiated base excision repair. Cancer cells also express high levels of MutT homolog 1 (MTH1), which prevents DNA replication-induced incorporation of 8-oxoG into the genome by hydrolyzing 8-oxo-7,8-dihydro-2\'-deoxyguanosine 5\'-triphosphate (8-oxo-dGTP). Here, we revealed that ROS-inducing agents triggered cervical cancer to undergo parthanatos, which was mainly induced by massive DNA strand breaks resulting from overwhelming 8-oxoG excision by OGG1. Furthermore, the MTH1 inhibitor synergized with a relatively low dose of ROS-inducing agents by enhancing 8-oxoG loading in the DNA. In vivo, this drug combination suppressed the growth of tumor xenografts, and this inhibitory effect was significantly decreased in the absence of OGG1. Hence, the present study highlights the roles of base repair enzymes in cell death induction and suggests that the combination of lower doses of ROS-inducing agents with MTH1 inhibitors may be a more selective and safer strategy for cervical cancer chemotherapy.

The presence of DNA damage can increase the likelihood of DNA replication errors and promote mutations. In particular, pauses of DNA polymerase at the site of damage can lead to polymerase slippage and the formation of 1-2-nucleotide bulges. Repair of such structures using an undamaged DNA template leads to small deletions. One of the most abundant oxidative DNA lesions, 8-oxoguanine (oxoG), was shown to induce small deletions, but the mechanism of this phenomenon is currently unknown. We studied the aberrant repair of oxoG located in one- and two-nucleotide bulges by the Escherichia coli and human base excision repair systems. Our results indicate that the repair in such substrates can serve as a mechanism for fixing small deletions in bacteria but not in humans.

Cardiovascular disease (CVD) is one of the leading causes of mortality worldwide, and multiple single‑nucleotide polymorphisms of DNA repair genes have been found to be associated with CVD. The aim of the present study was to assess the effects of the genetic variants of RAD51 recombinase (RAD51) and 8‑oxoguanine DNA glycosylase (OGG1) on CVD through genotyping and statistical analysis. Regardless of whether there is a significant association or not, the genotyping data on these two polymorphisms are valuable, because there is limited availability of it in certain populations. A total of 240 blood samples were analyzed and genotyped using TaqMan genotyping; 120 were obtained from cases with a history of CVD, and 120 from cases with no history of CVD. A questionnaire was administered to gather information on age, demographics, sex and clinical features, and confirmation was carried out using medical records. The results of the present study confirmed that the polymorphism rs1052133 in OGG1 had no significant association with CVD. On the other hand, the polymorphism rs1801321 in RAD51 exhibited a significant association with CVD. Collectively, the results of the present study revealed that the polymorphism rs1801321 in RAD51 exhibited a significant association with CVD, however a larger sample size to confirm the present findings, may allow for the early identification of CVD and may aid in the decision‑making process concerning treatments for CVD.

Cellular senescence is an important factor leading to pulmonary fibrosis. Deficiency of 8-oxoguanine DNA glycosylase (OGG1) in mice leads to alleviation of bleomycin (BLM)-induced mouse pulmonary fibrosis, and inhibition of the OGG1 enzyme reduces the epithelial mesenchymal transition (EMT) in lung cells. In the present study, we find decreased expression of OGG1 in aged mice and BLM-induced cell senescence. In addition, a decrease in OGG1 expression results in cell senescence, such as increases in the percentage of SA-β-gal-positive cells, and in the p21 and p-H2AX protein levels in response to BLM in lung cells. Furthermore, OGG1 promotes cell transformation in A549 cells in the presence of BLM. We also find that OGG1 siRNA impedes cell cycle progression and inhibits the levels of telomerase reverse transcriptase (TERT) and LaminB1 in BLM-treated lung cells. The increase in OGG1 expression results in the opposite phenomenon. The mRNA levels of senescence-associated secretory phenotype (SASP) components, including IL-1α, IL-1β, IL-6, IL-8, CXCL1/CXCL2, and MMP-3, in the absence of OGG1 are obviously increased in A549 cells treated with BLM. Interestingly, we demonstrate that OGG1 binds to p53 to inhibit the activation of p53 and that silencing of p53 reverses the inhibition of OGG1 on senescence in lung cells. Additionally, the augmented cell senescence is shown in vivo in OGG1-deficient mice. Overall, we provide direct evidence in vivo and in vitro that OGG1 plays an important role in protecting tissue cells against aging associated with the p53 pathway.

BACKGROUND: The role of DNA repair mechanisms is of significant importance in diseases characterized by elevated oxidative DNA damage, such as chronic kidney disease. It is imperative to thoroughly understand the functions of molecules associated with DNA repair mechanisms, not only for assessing susceptibility to diseases but also for monitoring disease progression. In this research, we investigated the APE1 and OGG1 gene expression levels, both of which are involved in the base excision repair (BER) mechanism in chronic hemodialysis patients with malignancy (HPM; n = 8) and without malignancy (HP; n = 36) in pre- and post-dialysis period and 37 healty persons. We also assessed how these values correlate with the clinical profiles of the patients.
RESULTS: We conducted gene expression analysis using real-time polymerase chain reaction (qRT-PCR). No significant differences in APE1 gene expression levels were observed in pre-dialysis when comparing the HP and HPM groups to the control group. The expression levels of the OGG1 gene were significantly lower in both the HP and HPM groups in pre- and post-dialysis periods compared to the control group. Dialysis procedures led to a reduction in APE1 and OGG1 gene expression levels in both HP and HPM groups.
CONCLUSIONS: The findings of our study elucidate the impact of alterations in the base excision repair (BER) mechanism, including the hemodialysis process, in end-stage renal disease (ESRD).

Oxidative stress-induced DNA base modifications, if unrepaired, can increase mutagenesis and genomic instability, ultimately leading to cell death. Cells predominantly use the base excision repair (BER) pathway to repair oxidatively-induced non-helix distorting lesions. BER is initiated by DNA glycosylases, such as 8-oxoguanine DNA glycosylase (OGG1), which repairs oxidatively modified guanine bases, including 7,8-dihydro-8-oxoguanine (8-oxoG) and ring-opened formamidopyrimidine lesions, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). The OGG1 protein contains a C2H2 zinc (Zn) finger DNA binding domain. However, the impact of dietary Zn deficiency on OGG1 catalytic activity has not been extensively studied. Zn is a common nutrient of concern with increasing age, and the prevalence of oxidative DNA damage is also concurrently increased during aging. Thus, understanding the potential regulation of OGG1 activity by Zn is clinically relevant. The present study investigates the impact of a range of Zn statuses, varying from severe Zn deficiency to exogenous Zn-supplementation, in the context of young and aged animals to determine the impact of dietary Zn-status on OGG1 activity and oxidative DNA damage in mice. Our findings suggest that nutritional Zn deficiency impairs OGG1 activity and function, without altering gene expression, and that aging further exacerbates these effects. These results have important implications for nutritional management of Zn during aging to mitigate age-associated DNA damage.