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Fapy•dG (N6-(2-deoxy-α,β-D-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine) and 8-OxodGuo (8-oxo-7,8-dihydro-2-deoxyguanosine) are major products of 2-deoxyguanosine oxidation. Fapy•dG is unusual in that it exists as a dynamic mixture of anomers. Much less is known about the effects of Fapy•dG than 8-OxodGuo on transcriptional bypass. The data presented here indicate that T7 RNA polymerase (T7 RNAP) bypass of Fapy•dG is more complex than that of 8-OxodGuo. Primer-dependent transcriptional bypass of Fapy•dG by T7 RNAP is hindered compared to 2-deoxyguanosine. T7 RNAP incorporates cytidine opposite Fapy•dG in a miniscaffold at least 13-fold more rapidly than A, G, or U. Fitting of reaction data indicates that Fapy•dG anomers are kinetically distinguishable. Extension of a nascent transcript past Fapy•dG is weakly dependent on the nucleotide opposite the lesion. The rate constants describing extension past fast- or slow-reacting base pairs vary less than twofold as a function of the nucleotide opposite the lesion. Promoter-dependent T7 RNAP bypass of Fapy•dG and 8-OxodGuo was carried out side by side. 8-OxodGuo bypass results in >55% A opposite it. When the shuttle vector contains a Fapy•dG:dA base pair, as high as 20% point mutations and 9% single-nucleotide deletions are produced upon Fapy•dG bypass. Error-prone bypass of a Fapy•dG:dC base pair accounts for ∼9% of the transcripts. Transcriptional bypass mutation frequencies of Fapy•dG and 8-OxodGuo measured in RNA products are comparable to or greater than replication errors, suggesting that these lesions could contribute to mutations significantly through transcription.

Objective: Mitochondrial DNA (mtDNA) depletion/deletions syndrome (MDDS) comprises a group of diseases caused by primary autosomal defects of mtDNA maintenance. Our objective was to study the etiology of MDDS in 4 patients who lack pathogenic variants in known genetic causes. Methods: Whole exome sequencing of the probands was performed to identify pathogenic variants. We validated the mitochondrial defect by analyzing mtDNA, mitochondrial dNTP pools, respiratory chain activities, and GUK1 activity. To confirm pathogenicity of GUK1 deficiency, we expressed 2 GUK1 isoforms in patient cells. Results: We identified biallelic GUK1 pathogenic variants in all 4 probands who presented with ptosis, ophthalmoparesis, and myopathic proximal limb weakness, as well as variable hepatopathy and altered T‐lymphocyte profiles. Muscle biopsies from all probands showed mtDNA depletion, deletions, or both, as well as reduced activities of mitochondrial respiratory chain enzymes. GUK1 encodes guanylate kinase, originally identified as a cytosolic enzyme. Long and short isoforms of GUK1 exist. We observed that the long isoform is intramitochondrial and the short is cytosolic. In probands' fibroblasts, we noted decreased GUK1 activity causing unbalanced mitochondrial dNTP pools and mtDNA depletion in both replicating and quiescent fibroblasts indicating that GUK1 deficiency impairs de novo and salvage nucleotide pathways. Proband fibroblasts treated with deoxyguanosine and/or forodesine, a purine phosphatase inhibitor, ameliorated mtDNA depletion, indicating potential pharmacological therapies. Interpretation: Primary GUK1 deficiency is a new and potentially treatable cause of MDDS. The cytosolic isoform of GUK1 may contribute to the T‐lymphocyte abnormality, which has not been observed in other MDDS disorders. ANN NEUROL 2024;96:1209–1224 [ABSTRACT FROM AUTHOR]

Introduction: Deoxyguanosine Kinase (DGUOK) deficiency is a very rare disorder characterized by liver dysfunction, neurological manifestations, and metabolic disorders secondary to severely reduced mitochondrial DNA content. These patients develop early-onset liver failure, and their liver transplantation (LT) indication remains debatable due to the possibility of neurological involvement. Case Report: We present the case of a 6-month-old female diagnosed with DGUOK deficiency who developed liver failure. At 9 months, she underwent a living-related LT with an initial favorable evolution under immunosuppression therapy with tacrolimus. Four months after LT, she presented two prolonged bacterial and Rotavirus enteritis episodes. She developed classical post-transplant complications (severe renal tubular acidosis type IV, secondary to the high tacrolimus level, and post-transplant lymphoproliferative disease) during these episodes. Her condition deteriorated progressively, with reversible hypotonia and significant weight loss. However, the neurological evaluation did not reveal any signs suggestive of the progression of the underlying disease. A few months later, her clinical features and laboratory parameters improved considerably. Conclusions: This case highlights the unpredictable evolution of children with LT for liver failure due to DGUOK deficiency. [ABSTRACT FROM AUTHOR]

Understanding the occurrence, repair, and biological consequences of DNA damage is important in environmental toxicology and risk assessment. The most common way to assess DNA damage elicited by exogenous sources in a laboratory setting is to expose cells or experimental animals with chemicals that modify DNA. Owing to the lack of reaction specificities of DNA damaging agents, the approach frequently does not allow for induction of a specific DNA lesion. Herein, we employed metabolic labeling to selectively incorporate N2-methyl-dG (N2-MedG) and N2-n-butyl-dG (N2-nBudG) into genomic DNA of cultured mammalian cells, and investigated how the levels of the two lesions in cellular DNA are modulated by different DNA repair factors. Our results revealed that nucleotide excision repair (NER) exert moderate effects on the removal of N2-MedG and N2-nBudG from genomic DNA. We also observed that DNA polymerases κ and η contribute to the incorporation of N2-MedG into genomic DNA and modulate its repair in human cells. In addition, loss of ALKBH3 resulted in higher frequencies of N2-MedG and N2-nBuG incorporation into genomic DNA, suggesting a role of oxidative dealkylation in the reversal of these lesions. Together, our study provided new insights into the repair of minor-groove N2-alkyl-dG lesions in mammalian cells.

Background: Deoxyguanosine kinase (DGUOK) deficiency is a rare mitochondrial disorder characterized by early onset liver failure and varying degrees of neurologic dysfunction. Patients typically present during infancy with progressive hepatic dysfunction leading to liver failure, which can precede neurologic deterioration. Outcomes posttransplantation are historically worse than average and the role of liver transplantation remains controversial. These factors, in combination with the increasing number of patients being diagnosed via molecular genetic testing, may impede waitlist access. Methods: We report our single‐center experience with three patients with DGUOK deficiency, all of whom were considered for transplant. We review the current literature regarding management and discuss the role of liver transplantation in DGUOK deficiency‐associated liver failure. Results: Two patients presented with hypoglycemia, conjugated hyperbilirubinemia, and lactic acidosis within the first week of life, were diagnosed with DGUOK deficiency prior to 2 months of age and had severe neurologic involvement. The third patient presented in later infancy was diagnosed with DGUOK deficiency at 18 months of age and had minimal neurologic involvement. All three patients were considered for transplant, though only two patients were listed. All three died from complications of end‐stage liver failure prior to liver transplantation between the ages of 5–20 months. Conclusion: Selection for liver transplantation in DGUOK deficiency is complex, requiring a multidisciplinary team approach. Recent data suggest that liver transplantation can be successful in select patients with absent or mild neurologic manifestations. National databases reporting long‐term outcomes posttransplantation are needed. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of serum s PLA2-X, 8-hydroxy-2’-deoxyguanosine, and hs CRP levels in diagnosing acute exacerbation of chronic obstructive pulmonary disease. Methods: A total of 128 COPD patients who underwent treatment in our hospital from March 2021 to November 2023 were randomly selected. The patients were divided into a stable group and an AECOPD group based on whether they experienced acute exacerbation. Among them, 29 were in the stable group and 99 were in the AECOPD group. Compare the differences in peripheral blood s PLA2-X, 8-OHd G, and hs CRP levels between the two groups of study subjects; The COX proportional risk factor regression model is used to analyze the influencing factors of AECOPD, and the ROC curve is used to analyze the value of related indicators for individual and combined detection and diagnosis of AECOPD. Results: The FEV1 index in the AECOPD group was significantly lower than that in the stable group, with a statistically significant difference （P＜0. 05）. Compared with the stable group, the peripheral blood s PLA2-X, 8-OHd G, and hs CRP levels in the AECOPD group were significantly increased, with statistical significance （P＜0. 01）. The levels of s PLA2-X, 8-Ohd G, and hs CRP in peripheral blood were positively correlated with GOLD grading （P＜0. 05）, while the levels of s PLA2-X, 8-Ohd G, and hs CRP in peripheral blood were negatively correlated with FEV1/FVC （%）and FEV1%pred（P＜0. 05）. Using the COX proportional risk factor regression model analysis, peripheral blood s PLA2-X, 8-Ohd G, and hs CRP were all independent risk factors affecting AECOPD. The area under the curve （AUC） of peripheral blood s PLA2-X, 8-Ohd G, and hs CRP in diagnosing AECOPD using ROC curve analysis were 0. 689, 0. 708, 0. 642, and 0. 875, respectively. The combined predictive value of each indicator was significantly higher than that of individual detection. Conclusion: The peripheral blood s PLA2-X, 8-Ohd G, and hs CRP levels in AECOPD patients are highly expressed. The levels of s PLA2-X, 8-Ohd G, and hs CRP in peripheral blood are correlated with the severity of lung function and lung function indicators, and can be used as potential predictive indicators for diagnosing acute exacerbation in COPD patients. The combination of the three has higher diagnostic value. [ABSTRACT FROM AUTHOR]

Background: Deoxyguanosine kinase deficiency is mainly manifested by hepatic and neurological damage, hence it belongs to the hepatocerebral form of mitochondrial deoxyribonucleic acid depletion syndrome. The association between deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax has not currently been reported. Case presentation: A 12-year-old Russian boy with deoxyguanosine kinase deficiency, a recipient of a liver transplant with amyotrophy secondary to his mitochondriopathy, presented with recurrent spontaneous bilateral pneumothorax refractory to drainage and surgery. Conclusion: To our knowledge, this is the first documented case of deoxyguanosine kinase deficiency associated with recurrent spontaneous pneumothorax, which could be considered a late complication of deoxyguanosine kinase deficiency. At this point, this is only an association and further studies and research need to be performed to help confirm the pathogenesis of this association. [ABSTRACT FROM AUTHOR]

We aimed to see the effect of lipids on 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA damage, and Interleukin-6 (IL-6), an inflammatory cytokine, in Diabetes Mellitus (DM) patients. Serum IL-6, and 8-OHdG levels were determined using kits based on the ELISA principle. The groups were different in terms of total cholesterol, LDL cholesterol and triglyceride. Group 2 (dyslipidemia positive DM positive) was significantly higher than the other groups. There was no statistical difference between group 1 (dyslipidemia negative DM positive) and the control group (p<0.001). 8-OHdG levels differ between groups. The level of 8-OHdG was significantly higher in group 2 compared to the other groups (p<0.001). IL-6 was different between groups. Group 2, IL-6 level was found to be significantly higher than the other groups (p<0.001). A positive correlation was found between serum 8-OHdG level and total cholesterol (r=0.417 p<0.001), LDL cholesterol (r=0.491 p<0.001) and triglyceride (r=0.441 p<0.001). A positive correlation was found between IL-6 and total cholesterol (r=0.522 p<0.001), LDL cholesterol (r=0.646 p<0.001) and triglyceride (r=0.495 p<0.001). IL-6 and 8-OHdG levels are high in dyslipidemic DM patients with a high lipid profile. IL-6 and 8-OHdG levels are elevated in dyslipidemic DM patients with a high lipid profile. IL-6 and 8-OHdG can be used as biomarkers to evaluate dyslipidemic complications seen in DM patients in the early diagnosis. [ABSTRACT FROM AUTHOR]

Recently, 1,5-anhydro-D-glucitol (1,5-AG) has been manufactured using microbe-derived enzymes and we previously reported that it inhibits intestinal sucrase and maltase activity. However, its function in supplements for diabetes prevention has not been clarified. We investigated the effect feeding of 1,5-AG has of delaying the onset of diabetes through its antioxidant properties. KKAy mice were raised with an AIN93G (control), 3 % or 6 % 1,5-AG, or 6 % erythritol (ERT, positive control) diet for 7 weeks. Urinary glucose excretion in the 6 % 1,5-AG group at 4 and 6 weeks and in the 6 % ERT group at 4, 6, and 7 weeks was significantly lower than in the control group (p < 0.05). After 7 weeks, urine 8-hydroxy-2’- deoxyguanosine, fasting plasma glucose, insulin, total cholesterol, and triacylglycerol in the 6 % 1,5-AG group were lower than in the control group (p < 0.05). Feeding of 6 % 1,5-AG appears to prevent the onset of diabetes-related symptoms through its systemic antioxidant effect. [ABSTRACT FROM AUTHOR]

Acrylamide, a common food contaminant, is metabolically activated to glycidamide, which reacts with DNA at the N7 position of dG, forming N7-(2-carbamoyl-2-hydroxyethyl)-dG (GA7dG). Owing to its chemical lability, the mutagenic potency of GA7dG has not yet been clarified. We found that GA7dG undergoes ring-opening hydrolysis to form N6-(2-deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-[N-(2-carbamoyl-2-hydroxyethyl)formamido]pyrimidine (GA-FAPy-dG), even at neutral pH. Therefore, we aimed to examine the effects of GA-FAPy-dG on the efficiency and fidelity of DNA replication using an oligonucleotide carrying GA-FAPy–9-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)guanine (dfG), a 2′-fluorine substituted analog of GA-FAPy-dG. GA-FAPy-dfG inhibited primer extension by both human replicative DNA polymerase ε and the translesion DNA synthesis polymerases (Polη, Polι, Polκ, and Polζ) and reduced the replication efficiency by less than half in human cells, with single base substitution at the site of GA-FAPy-dfG. Unlike other formamidopyrimidine derivatives, the most abundant mutation was G:C > A:T transition, which was decreased in Polκ- or REV1-KO cells. Molecular modeling suggested that a 2-carbamoyl-2-hydroxyethyl group at the N5 position of GA-FAPy-dfG can form an additional H-bond with thymidine, thereby contributing to the mutation. Collectively, our results provide further insight into the mechanisms underlying the mutagenic effects of acrylamide. [ABSTRACT FROM AUTHOR]

Abstract Background Frequent heavy air pollution occurred during the winter heating season of northern China. Particulate air pollution is a serious concern in Urumqi during heating season. Exposure to air pollution is known to increase adverse health outcomes, particularly oxidative damage. This study aimed to evaluate the impact of air pollution on oxidative damage around pregnant women and newborns in Urumqi. Methods This prospective observational study enrolled pregnant women in the Fifth Affiliated Hospital of Xinjiang Medical University between January 2019 and October 2019. Pregnant women and newborns were allocated into a heating season group (January - end of April 2019, October 2019) or non-heating season group (June 2019 - end of September) according to the specific delivery time. Venous blood, urine from the women and cord blood from their newborns were collected to measure the levels of PAHs and 8-deoxyguanosine (8-OHdG), a measure of oxidative stress. Results A total of 200 pregnant women and newborns were enrolled, with 100 pregnant women and newborns in the heating season group. Compared to the non-heating season group, the total contents of 8-OHdG in maternal urine, PAHs and 8-OHdG in maternal plasma and neonatal cord blood were higher in the heating season group (all P

Cladribine is a deoxyadenosine analog prodrug originally developed to treat hairy-cell leukemia and other lymphoproliferative diseases. However, it is now primarily used in the treatment of relapsing types of multiple sclerosis (MS). Understanding how medications interact with dsDNA is crucial for developing more effective and efficient medications. This study aims to examine the binding behavior of cladribine with dsDNA via various analytical methods, such as heat denaturation, UV spectroscopy, fluorescence spectroscopy, electrochemistry, and viscosity tests. The binding constant (K b) of cladribine with dsDNA has been estimated to be 2.41 × 104 ± 0.20 at 298 K using the Benesi-Hildebrand plot. Molecular docking simulations were employed to explore the dsDNA-cladribine interactions quantitatively at the molecular level. Molecular Dynamic simulations were performed to follow the stability of drug-bound DNA for 50 ns. The simulations revealed that cladribine binds to dsDNA via the minor groove region of DNA by forming hydrogen bonds mainly with Guanine's DNA bases. The post-MD analyses enabled us to follow the stability of DNA and cladribine complex. Additionally, two methods based on the electrochemical approach were developed in this study for low-level cladribine assessment using differential pulse voltammetry (DPV). The first method relies on cladribine oxidation in pH 2 phosphate buffer, while the second method uses deoxyguanosine oxidation signals resulting from cladribine and dsDNA binding in pH 4.80 acetate buffer. The analytical efficacy of the two methods was verified using cladribine concentrations ranging from 2 to 25 μM, with a limit of detection (LOD) of 0.30 and 0.92 μM, respectively. Furthermore, the study conducted percent recovery tests by employing pharmaceutical injection using both established methodologies. [ABSTRACT FROM AUTHOR]

Through the utilization of fluorescence spectroscopy, electrochemical, and molecular docking methods, this research investigates the interaction between the antihistamine drug desloratadine and calf thymus double-stranded DNA (ct-dsDNA). Deoxyguanosine (dGuo) and deoxyadenosine (dAdo) oxidation signals were diminished by incubation with varying concentrations of desloratadine, as determined by differential pulse voltammetry (DPV). This change was ascribed to desloratadine's binding mechanism to ct-dsDNA. The binding constant (K b) between desloratadine and ct-dsDNA was determined to be 2.2 × 105 M−1 throughout electrochemical experiments. In order to further develop our comprehension of the interaction mechanism between desloratadine and ct-dsDNA, a series of spectroscopic experiments and molecular docking simulations were conducted. The K b value was found to be 8.85 × 104 M−1 at a temperature of 25 °C by the use of fluorescence spectroscopic techniques. In summary, the utilization of electrochemical and spectroscopic techniques, alongside molecular docking investigations, has led to the prediction that desloratadine has the capability to interact with ct-dsDNA by groove binding. [Display omitted] • The DNA and Desloratadine interaction was investigated for the first time by voltammetric, spectroscopic and molecular modeling techniques. • The binding event's thermodynamic profile and binding constant are determined. • Molecular docking substantiates the groove-binding mode of interaction. • The interaction mechanism proposed by computational approaches provides a good depiction of the electrochemical interaction. [ABSTRACT FROM AUTHOR]

Understanding the dose-response for formaldehyde-induced nasal cancer in rats is complicated by (1) the uneven distribution of inhaled formaldehyde across the interior surface of the nasal cavity and, (2) the presence of endogenous formaldehyde (endoF) in the nasal mucosa. In this work, we used computational fluid dynamics (CFD) modeling to predict flux of inhaled (exogenous) formaldehyde (exogF) from air into tissue at the specific locations where DNA adducts were measured. Experimental work has identified DNA-protein crosslink (DPX) adducts due to exogF and deoxyguanosine (DG) adducts due to both exogF and endoF. These adducts can be considered biomarkers of exposure for effects of endoF and exogF on DNA that may be part of the mechanism of tumor formation. We describe a computational model linking CFD-predicted flux of formaldehyde from air into tissue, and the intracellular production of endoF, with the formation of DPX and DG adducts. We assumed that, like exogF, endoF can produce DPX. The model accurately reproduces exogDPX, exogDG, and endoDG data after inhalation from 0.7 to 15 ppm. The dose-dependent concentrations of exogDPX and exogDG are predicted to exceed the concentrations of their endogenous counterparts at about 2 and 6 ppm exogF, respectively. At all concentrations examined, the concentrations of endoDPX and exogDPX were predicted to be at least 10-fold higher than that of their DG counterparts. The modeled dose-dependent concentrations of these adducts are suitable to be used together with data on the dose-dependence of cell proliferation to conduct quantitative modeling of formaldehyde-induced rat nasal carcinogenicity. [ABSTRACT FROM AUTHOR]

[Display omitted] Co-crystallization of active pharmaceutical ingredients (API) with co-formers can induce synergistic effects on cytotoxicity; however, the underlying mechanism is unclear. Here, cell metabolomics was used to gain insight into the mechanisms of synergistic effect from API and co-former in co-crystal. The 5-Fluorouracil-phenylalanine co-crystal system was selected as the model owing to the apparent difference of cytotoxicity occurring between co-crystal and physical mixture of two components (PM). The cytotoxicity of 5-FU, PM and co-crystal on B16 cells were evaluated by MTT assay. Based on the IC 50 values from MTT assays, the cytotoxicity mechanism of 5-FU, PM and co-crystal was evaluated using a comprehensive non-targeted metabolomics strategy based on multivariate data analysis and statistics using UHPLC-Q-TOF-MS/MS platform with IDA data acquisition. Co-crystal showed higher cytotoxicity than PM against B16 cells. In the cell metabolomics study, a total of 12 differential metabolites were found. Pathway analysis indicated that differences in purine and glycerophospholipid metabolism occurred between PM and co-crystal. The downregulated deoxyguanosine diphosphate and adenosine diphosphate in the purine metabolism and downregulated L-glycerophosphocholine and upregulated C16-dihydroceramide in the glycerophospholipid metabolism were associated with cellular antiproliferation and apoptosis, which directly influenced the cytotoxicity. Cell metabolomics was used to investigate the cytotoxicity mechanism of the pharmaceutical co-crystal, providing an effective and innovative method for clarifying the synergistic mechanism of API and CCF in co-crystal. [ABSTRACT FROM AUTHOR]

Abstract Introduction Recently, it was revealed that uric acid is a photosensitizer of reactions of nucleosides on irradiation with UV light at wavelengths longer than 300 nm, and two products generated from 2′-deoxycytidine were identified. In the present study, UV reactions of acetylated derivatives of 2′-deoxyguansoine and 2′-deoxyadenosine were conducted and their products were identified. Findings Each reaction of 3′,5′-di-O-acetyl-2′-deoxyguansoine or 3′,5′-di-O-acetyl-2′-deoxyadenosine with UV light at wavelengths longer than 300 nm in the presence of uric acid generated several products. The products were separated by HPLC and identified by comparing UV and MS spectra of the products with previously reported values. The major products were spiroiminodihydantoin, imidazolone, and dehydro-iminoallantoin nucleosides for 3′,5′-di-O-acetyl-2′-deoxyguansoine, and an adenine base and a formamidopyrimidine nucleoside for 3′,5′-di-O-acetyl-2′-deoxyadenosine. Conclusions If these damages caused by uric acid with sunlight occur in DNA of skin cells, mutations may arise. We should pay attention to the genotoxicity of uric acid in terms of DNA damage to dGuo and dAdo sites mediated by sunlight.

The research on DNA adduct 8-OHdG formation is performed by reacting 2'-deoxyguanosine and H2O2 with acrylamide (AA) and TBHQ compounds that were exposed to UVA light. The 8-OHdG forming test was conducted at various incubation times (5 h and 7 h) and pH variations (7.4 and 8.4). The 8-OHdG formation was analyzed using a reversed-phase HPLC instrument using a buffer solution of sodium phosphate pH 6.7: methanol (85:15) as eluent. The results showed that samples containing TBHQ and acrylamide (AA) produced 8-OHdG and shows synergistic and antagonistic effects. The 8-OHdG level of mixing acrylamide (AA) and TBHQ compounds increased significantly when exposed to UVA light. Samples incubated with UVA exposure had higher levels of 8-OHdG than samples without UVA exposure. The longer the incubation time, the greater the 8-OHdG content was produced. At pH 8.4, most of the samples resulted in greater 8-OHdG formation when compared to samples with the same mixture at pH 7.4. Samples with the greatest 8-OHdG formation results were found in samples containing 2'-deoxyguanosine, acrylamide (AA), TBHQ, and H2O2 at pH 8.4 with UVA light irradiation for 7h [ABSTRACT FROM AUTHOR]

Nanomaterials or nanoparticles are commonly used in the cosmetics, medicine, and food industries. Many researchers studied the possible side effects of several nanoparticles including aluminum oxide (Al2O3-nps) and zinc oxide nanoparticles (ZnO-nps). Although, there is limited information available on their direct or side effects, especially on the brain, heart, and lung functions. This study aimed to investigate the neurotoxicity, cardiotoxicity, and lung toxicity induced by Al2O3-nps and ZnO-nps or in combination via studying changes in gene expression, alteration in cytokine production, tumor suppressor protein p53, neurotransmitters, oxidative stress, and the histological and morphological changes. Obtained results showed that Al2O3-nps, ZnO-nps and their combination cause an increase in 8-hydroxy-2´-deoxyguanosine (8-OHdG), cytokines, p53, oxidative stress, creatine kinase, norepinephrine, acetylcholine (ACh), and lipid profile. Moreover, significant changes in the gene expression of mitochondrial transcription factor-A (mtTFA) and peroxisome proliferator activator receptorgamma-coactivator-1α (PGC-1α) were also noted. On the other hand, a significant decrease in the levels of antioxidant enzymes, total antioxidant capacity (TAC), reduced glutathione (GSH), paraoxonase 1 (PON1), neurotransmitters (dopamine – DA, and serotonin – SER), and the activity of acetylcholine esterase (AChE) in the brain, heart, and lung were found. Additionally, these results were confirmed by histological examinations. The present study revealed that the toxic effects were more when these nanoparticle doses are used in combination. Thus, Al2O3-nps and ZnO-nps may behave as neurotoxic, cardiotoxic, and lung toxic, especially upon exposure to rats in combination. [ABSTRACT FROM AUTHOR]

Deoxyguanosine kinase deficiency is one genetic cause of mtDNA depletion syndrome. Its major phenotypes include neonatal/infantile-onset hepatocerebral disease, isolated hepatic disease and myopathic disease. In this retrospective study, we seek to describe the natural history of deoxyguanosine kinase deficiency and identify any genotype-phenotype correlations. Retrospective literature search and collation of data from genetically confirmed cases of deoxyguanosine kinase deficiency. 173 cases of DGUOK deficiency were identified. Neonatal/infantile-onset hepatocerebral disease accounted for 128 (74%) of cases. Isolated liver disease was seen in 36 (21%) and myopathic disease in 9 (5%) of cases. The most frequently involved systems were liver (98%), brain (75%), growth (46%) and gastrointestinal tract (26%). Infantile-onset disease typically presented with cholestatic jaundice and lactic acidosis. Neurological involvement included hypotonia, nystagmus and developmental delay with MRI brain abnormalities in about half of cases. Missense variants accounted for 48% of all pathogenic variants while variants resulting in truncated transcripts accounted for 39%. Prognosis was poor, especially for neonatal/ infantile-onset hepatocerebral disease for which 1 year survival was 11%. Twenty-three patients received liver transplants, of whom 12 died within 2 years of transplant. Patients with two truncating variants had a higher risk of death and were more likely to have the neonatal/infantile-onset hepatocerebral disease phenotype. No blood biomarker predictive of neurological involvement was identified. Earlier onset correlated with increased mortality. There is a narrow window for therapeutic intervention. For the hepatocerebral disease phenotype, median age of onset was 1 month while the median age of death was 6.5 months implying rapid disease progression. [ABSTRACT FROM AUTHOR]

N,O‐Diacetyl tyrosine and 3‐(4‐hydroxy‐phenyl)‐propanoic acid were converted into phosphoramidite derivatives and introduced to the 5′‐end of oligonucleotides. The resulting oligonucleotides exhibiting a 4‐hydroxyphenyl alkyl group were conjugated with 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione as a model of a Y‐click reaction. The reaction is fast (<1 h) and efficient (>90 %). A partial side reaction occurred at the C8 position of deoxyguanosine in single‐stranded oligonucleotides. This side reaction does not take place on the G quadruplex and double‐stranded oligonucleotides and when N2 position of guanine is protected. This Y‐click reaction could be applied to 1,2,4‐triazoline‐3,5‐dione derivatives displaying a fluorescent dye, a carbohydrate or orthogonal functions (alkyne, azide, ketone or maleimide) for the labelling of oligonucleotides. [ABSTRACT FROM AUTHOR]

Objective: Oxidative stress has been shown to play a role in the pathophysiology of several diseases, making it a popular yet contentious research area. There is some evidence that selective melanocyte destruction may have developed in vitiligo patients as a result of elevated oxidative stress. The purpose of this study is to investigate the impact of oxidative stress on lipid, protein, and nucleic acid metabolism in vitiligo patients. Methods: We used ELISA method to measure serum oxidative stress markers in patients with generalized vitiligo who had newly formed lesions in the previous three months but had not been treated, as well as healthy controls. Malondialdehyde (MDA), 2,4-dinitrophenyl hydrazone (DNPH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and uncoupling protein 2 (UCP2) levels were measured to assess the influence of reactive oxygen derivatives on lipid, protein, nucleic acid metabolism, and mitochondria, respectively. Results: The study included 84 participants, including 64 active generalized vitiligo patients and 20 healthy controls with similar age and gender distribution. In the serum of vitiligo patients, we detected significantly lower levels of MDA (ng/mL, mean±SD=12±19; 33.4±35.9), DNPH (ng/mL, mean±SD=2±3.1; 6±7.4), 8-OHdG (ng/mL, mean±SD=11.7±17.9; 32.7±37) and UCP2 (ng/mL, mean±SD=8.7±13.7; 21.5±28.4. Conclusions: Although there is significant evidence that oxidative stress plays a role in the pathophysiology of vitiligo, the studies should be interpreted cautiously due to the heterogeneity in the methodology, complexity of the oxidative stress pathways, and potential publication bias. Large-scale studies using a standardized methodology are required to determine how significant oxidative stress is in the core pathophysiology of vitiligo and which pathways it primarily affects. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to examine thiol/disulfide homeostasis and oxidative DNA damage in patients with OCD and compare them with healthy controls. Methods: Thirty-five patients previously diagnosed with OCD in Van Yuzuncu Yil University Department of Psychiatry and thirty-three healthy volunteers were included in the study. The severity of the symptoms was measured using the Yale-Brown Obsessive-Compulsive Scale. Five ml of blood samples were taken from the patient and control groups. The samples were stored at appropriate conditions until use. Leukocyte DNA was isolated and the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and deoxyguanosine were detected to assess the oxidative DNA damage. The level of oxidative DNA damage was expressed as 8-OHdG/106dG. Total thiol/native thiol levels were measured for thiol/disulfide homeostasis. The level of disulfide was determined by subtracting the native thiol value from the total thiol value and the result was divided by two. Results were given as percentages. Results: The total and native thiol levels in patients with OCD were significantly lower, and the disulfide levels were significantly higher in patients with OCD than healthy control subjects. In addition, 8-OHdG, an indicator of DNA damage, was significantly lower in the control group compared to the patient group. Conclusion: Increased levels of disulfide/native thiol and disulfide/total thiol in patients with OCD show that levels of oxidative stress were elevated and therefore, higher 8-OHdG levels in patients with OCD is a marker of oxidative DNA damage. [ABSTRACT FROM AUTHOR]

Deoxyguanosine kinase (dGK) is reported responsible for the phosphorylation of deoxyadenosine (dA) and deoxyguanosine (dG) in the mitochondrial purine salvage pathway. Antiviral nucleoside analogs known as nucleoside reverse transcriptase inhibitors (NRTIs) must be phosphorylated by host enzymes for the analog to become active. We address the possibility that NRTI purine analogs may be competitive inhibitors of dGK. From a group of such analogs, we demonstrate that entecavir (ETV) competitively inhibited the phosphorylation of dG and dA in rat mitochondria. Mitochondria from the brain, heart, kidney, and liver showed a marked preference for phosphorylation of dG over dA (10-30-fold) and ETV over dA (2.5-4-fold). We found that ETV inhibited the phosphorylation of dG with an IC50 of 15.3 ± 2.2 μM and that ETV and dG were both potent inhibitors of dA phosphorylation with IC50s of 0.034 ± 0.007 and 0.028 ± 0.006 μM, respectively. In addition, the phosphorylation of dG and ETV followed Michaelis-Menten kinetics and each competitively inhibited the phosphorylation of the other. We observed that the kinetics of dA phosphorylation were strikingly different from those of dG phosphorylation, with an exponentially lower affinity for dGK and no effect of dA on dG or ETV phosphorylation. Finally, in an isolated heart perfusion model, we demonstrated that dG, dA, and ETV were phosphorylated and dG phosphorylation was inhibited by ETV. Taken together, these data demonstrate that dGK is inhibited by ETV and that the primary role of dGK is in the phosphorylation of dG rather than dA. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to determine the prognostic value of 8-oxo-2'-deoxyguanosine (8-OHdG) plasma levels for cardiovascular complications (CVC) development in hypertension (HTN) and type 2 diabetes mellitus (T2DM) comorbidity. Material and methods: One hundred fifty-six patients (mean age 61.71 ± 0.87 years) with the combined course of HTN stage II and T2DM (group 1) and 100 non-diabetic patients with HTN stage II (mean age 60.59 ± 0.87 years, group 2) were examined. Lipid, carbohydrate metabolism, plasma insulin, plasma 8-OHdG (by ELISA), blood pressure levels were measured. Observation period was 12 months. Results: Plasma levels of 8-OHdG in the patients' groups were significantly higher than in the controls (p < 0.001), in the group 1 higher than in group 2 (15.37 ± 0.27 ng/L vs. 14.00 ± 0.29 ng/L, respectively, p = 0.002). Plasma levels of 8-OHdG in group-2 patients who developed cardiovascular complications during observation period were significantly higher than in those without cardiovascular complications (16.47 ± 0.62 ng/L vs. 15.11 ± 0.29 ng/L, respectively, p = 0.046). The ROC analysis made it possible to propose the 8-OHdG plasma level = 15.68 ng/L as an identifier for the cardiovascular complications in patients with studied comorbidity. In group 1, in patients with 8-OHdG plasma level = 15.68 ng/L such cardiovascular risk factors as total cholesterol (TC) (p = 0.034), low density lipoprotein cholesterol (LDL-C) (p = 0.035), systolic blood pressure (p = 0.022), HOMA-IR (p = 0.046) were significantly higher compared with those whose level of this indicator was < 15.68 ng/L. Conclusion: Determination of the plasma 8-OHdG allows not only for assessment of the severity of oxidative stress, but also for determination of the course and prognosis in comorbidity of HTN and T2DM. [ABSTRACT FROM AUTHOR]

Adenosine synthase A (AdsA) is a key virulence factor of Staphylococcus aureus , a dangerous microbe that causes fatal diseases in humans. Together with staphylococcal nuclease, AdsA generates deoxyadenosine (dAdo) from neutrophil extracellular DNA traps thereby igniting caspase-3-dependent cell death in host immune cells that aim at penetrating infectious foci. Powered by a multi-technological approach, we here illustrate that the enzymatic activity of AdsA in abscess-mimicking microenvironments is not restricted to the biogenesis of dAdo but rather comprises excessive biosynthesis of deoxyguanosine (dGuo), a cytotoxic deoxyribonucleoside generated by S. aureus to eradicate macrophages of human and animal origin. Based on a genome-wide CRISPR-Cas9 knock-out screen, we further demonstrate that dGuo-induced cytotoxicity in phagocytes involves targeting of the mammalian purine salvage pathway-apoptosis axis, a signaling cascade that is concomitantly stimulated by staphylococcal dAdo. Strikingly, synchronous targeting of this route by AdsA-derived dGuo and dAdo boosts macrophage cell death, indicating that S. aureus multiplexes death-effector deoxyribonucleosides to maximize intra-host survival. Overall, these data provide unique insights into the cunning lifestyle of a deadly pathogen and may help to design therapeutic intervention strategies to combat multidrug-resistant staphylococci. [ABSTRACT FROM AUTHOR]

Adenosine synthase A (AdsA) is a key virulence factor of Staphylococcus aureus, a dangerous microbe that causes fatal diseases in humans. Together with staphylococcal nuclease, AdsA generates deoxyadenosine (dAdo) from neutrophil extracellular DNA traps thereby igniting caspase-3-dependent cell death in host immune cells that aim at penetrating infectious foci. Powered by a multi-technological approach, we here illustrate that the enzymatic activity of AdsA in abscess-mimicking microenvironments is not restricted to the biogenesis of dAdo but rather comprises excessive biosynthesis of deoxyguanosine (dGuo), a cytotoxic deoxyribonucleoside generated by S. aureus to eradicate macrophages of human and animal origin. Based on a genome-wide CRISPR-Cas9 knock-out screen, we further demonstrate that dGuo-induced cytotoxicity in phagocytes involves targeting of the mammalian purine salvage pathway-apoptosis axis, a signaling cascade that is concomitantly stimulated by staphylococcal dAdo. Strikingly, synchronous targeting of this route by AdsA-derived dGuo and dAdo boosts macrophage cell death, indicating that S. aureus multiplexes death-effector deoxyribonucleosides to maximize intra-host survival. Overall, these data provide unique insights into the cunning lifestyle of a deadly pathogen and may help to design therapeutic intervention strategies to combat multidrug-resistant staphylococci.

Introduction: Recently, it was revealed that uric acid is a photosensitizer of reactions of nucleosides on irradiation with UV light at wavelengths longer than 300 nm, and two products generated from 2′-deoxycytidine were identified. In the present study, UV reactions of acetylated derivatives of 2′-deoxyguansoine and 2′-deoxyadenosine were conducted and their products were identified. Findings: Each reaction of 3′,5′-di-O-acetyl-2′-deoxyguansoine or 3′,5′-di-O-acetyl-2′-deoxyadenosine with UV light at wavelengths longer than 300 nm in the presence of uric acid generated several products. The products were separated by HPLC and identified by comparing UV and MS spectra of the products with previously reported values. The major products were spiroiminodihydantoin, imidazolone, and dehydro-iminoallantoin nucleosides for 3′,5′-di-O-acetyl-2′-deoxyguansoine, and an adenine base and a formamidopyrimidine nucleoside for 3′,5′-di-O-acetyl-2′-deoxyadenosine. Conclusions: If these damages caused by uric acid with sunlight occur in DNA of skin cells, mutations may arise. We should pay attention to the genotoxicity of uric acid in terms of DNA damage to dGuo and dAdo sites mediated by sunlight. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of the study was to examine the possible effects of curcumin on the formation of neomucosa in parietal peritoneum which was applied as a patch for terminal ileal defect in rats. Methods: Sixteen male Wistar Hannover rats were split into two groups. The control group was injected with saline and curcumin (2 mL/kg/day, by gavage) was given to the experimental group. In both groups, amounts of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), the activities of glutathione peroxidase and superoxide dismutase were determined in serum. The development of neomucosa formation was examined morphologically. Results: Serum antioxidant levels and glutathione peroxidase activity in rats given curcumin were significantly higher than those of the control group (p<0.05). The levels of oxidative markers (MDA and 8-OHdG) in rats given curcumin were significantly lower than those of the control group (p<0.05). In the histopathological examination, 62.5% of rats in the curcumin group showed formation of neomucosa while 37.5% of control rats showed neomucosa. Conclusion: The use of curcumin in rats with terminal ileal defect enhanced the formation of neomucosa by decreasing the oxidation level and increasing the antioxidation level. Curcumin may be used in the patients with short bowel syndrome to increase the absorption surface area. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) is a situation that occurs as a result of un-equilibrium between reactive oxygen species (ROS) formation and the antioxidant defence system. 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidized form of deoxyguanosine, is found in higher levels in aging oocytes. In this cross-sectional study, we aimed to evaluate the effect of 8-OHdG on the intracytoplasmic sperm injection (ICSI). Follicular fluid (FF) samples were taken after removing the oocyte for later analysis of 8-OHdG. The couples participants were categorized according to the cause of subfertility into three groups (female factor, malefactor, and unexplained infertility). Further division according to pregnancy state was done to evaluate the precise role of 8-OHdG on pregnancy state and ICSI outcome. Result : This study showed that the 8-OHdG levels significantly higher in non-pregnant women (p < 0.05). Correlation study showed that 8-OHdG level in follicular fluid is negatively correlating with the number of retrieved oocytes, metaphase two oocytes (MII), fertilized oocytes (2PN = two pronuclei), cleaved zygotes, good quality embryos, and the difference was statistically significant (p < 0.05). Conclusion: The study revealed that the 8-OHdG level in follicular fluid negatively influences ICSI outcome and it is higher in non-pregnant women. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polarization of the water environment reduces double-ionization energies and facilitates the hole transfer. • Double ionization in solutions is independent of the counterion. • The environment screens the contribution of the phosphate group. • The barrier height of bond break suggests that the scission of the glycosidic bond could be a potential damaged pathway. Computations were carried out to investigate the mechanism of double-ionization damage for deoxyguanosine nucleotide. The results reveal that the polarization of the water environment reduces double-ionization energies and facilitates the hole transfer. Double ionization in solutions is independent of the counterion. The environment screens the contribution of the phosphate group. After double ionization, cleavage of the C-N glycosidic bond is a barrierless process in the gas phase. The barrier height of bond break is ∼ 4.0 kcal/mol in solutions. The C-N scission could be a potential damaged pathway. The counterion has a minor effect on the bond rupture. [ABSTRACT FROM AUTHOR]

Small structural alterations of the purine/pyrimidine core have been related to important photophysical changes, such as the loss of photostability. Similarly to canonical nucleobases, solute-solvent interactions can lead to a change in the excited state lifetimes and/or to the interplay of different states in the photophysics of these modified nucleobases. To shed light on both effects, we here report a complete picture of the absorption spectra and excited state deactivation of deoxyguanosine and its closely related derivative, deoxydeazaguanosine, in water and methanol through the mapping of the excited state potential energy surfaces and molecular dynamics simulations at the TD-DFT level of theory. We show that the N by CH exchange in the imidazole ring of deoxyguanosine translates into a small red-shift of the bright states and slightly faster dynamics. In contrast, changing solvent from water to methanol implies the opposite, i.e., that the deactivation of both systems to the ground state is significantly hindered.

Oxidative DNA lesions cause significant detrimental effects on a living species. Two major DNA lesions resulting from dG oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo) and formamidopyrimidine (Fapy·dG), are produced from a common chemical intermediate. Fapy·dG is formed in comparable yields under oxygen-deficient conditions. Replicative bypass of Fapy·dG in human cells is more mutagenic than that of 8-OxodGuo. Despite the biological importance of transcriptional mutagenesis, there are no reports of the effects of Fapy·dG on RNA polymerase II (Pol II) activity. Here we perform comprehensive kinetic studies to investigate the impact of Fapy·dG on three key transcriptional fidelity checkpoint steps by Pol II: insertion, extension, and proofreading steps. The ratios of error-free versus error-prone incorporation opposite Fapy·dG are significantly reduced in comparison with undamaged dG. Similarly, Fapy·dG:A mispair is extended with comparable efficiency as that of the error-free, Fapy·dG:C base pair. The α- and β-configurational isomers of Fapy·dG have distinct effects on Pol II insertion and extension. Pol II can preferentially cleave error-prone products by proofreading. To further understand the structural basis of transcription processing of Fapy·dG, five different structures were solved, including Fapy·dG template-loading state (apo), error-free cytidine triphosphate (CTP) binding state (prechemistry), error-prone ATP binding state (prechemistry), error-free Fapy·dG:C product state (postchemistry), and error-prone Fapy·dG:A product state (postchemistry), revealing distinctive nucleotide binding and product states. Taken together, our study provides a comprehensive mechanistic framework for better understanding how Fapy·dG lesions impact transcription and subsequent pathological consequences.

One of the most distinguished features in biological effects of heavy ions would be the decrease of oxygen effect in the high-LET region. This feature has been referred to as the radiobiological basis for the control of hypoxic fraction in cancer radiotherapy. However, mechanisms to explain this phenomenon have not been fully understood. One of the explanations was given by the oxygen in the track hypothesis, which proposes that oxygen is produced along ion tracks even in the hypoxic irradiation condition. In the present study, we designed an experimental approach to support this hypothesis by using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as DNA damage requiring oxygen to produce. The LET dependence of 8-OHdG under hypoxic condition revealed that with increasing LET 8-OHdG yield seems to increase, despite that the yield of OH radical, which is also required for the production of 8-OHdG, decreases in the high-LET region. This result is consistent with the explanation that the local generation of oxygen along ion tracks contributes to the increase of 8-OHdG yield., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

In recent years, research has shown that oxidative stress plays a significant role in chronic inflammatory conditions. The alteration of the oxidant/antioxidant balance leads to the appearance of free radicals, important molecules involved in both diabetes mellitus and periodontal disease. Diabetes is considered to be one of the major risk factors of periodontal disease and the inflammation characterizing this condition is associated with oxidative stress, implicitly resulting in oxidative damage to DNA. 8-Hydroxydeoxyguanosine (8-OHdG) is the most common stable product of oxidative DNA damage caused by reactive oxygen species, and its levels have been reported to increase in body fluids and tissues during inflammatory conditions. 8-OHdG emerges as a pivotal biomarker for assessing oxidative DNA damage, demonstrating its relevance across diverse health conditions, including neurodegenerative disorders, cancers, inflammatory conditions, and periodontal disease. Continued research in this field is crucial for developing more precise treatments and understanding the detailed link between oxidative stress and the progression of periodontitis. The use of the 8-OHdG biomarker in assessing and managing chronic periodontitis is an area of increased interest in dental research, with the potential to provide crucial information for diagnosis and treatment.

In this study, experimental studies were carried out to explore the action mechanism of the anti-cancer drug Azacitidine on the double-stranded DNA (dsDNA). The drug binding constant (K b ) was found to be 4.13 ± 0.23 × 10 5 M -1 using voltammetric measurements and 1.67 ± 0.24 × 10 5 M -1 using the fluorescence spectroscopy. Both values are close to the values of 2.04 ± 0.30 × 10 5 M -1 for deoxyguanosine (dGuO) and 1.23 ± 0.30 × 10 5 M -1 for deoxyadenosine (dAdo). In the displacement studies, the ethidium bromide, strong DNA intercalator, was replaced by the Azacitidine, hence caused a decrease on the fluorescence emission intensity. In thermal denaturation studies, the increase of 8.60 °C in the melting temperature upon introduction of the Azacitidine into the dsDNA solution cleary indicated intercalation binding mode of the drug. The experimental and theoretical IR spectra of Azacitidine, dsDNA and their H-bonded complex were confirmed the Azacitidine's intercalation ability to induce cytotoxicity. We also developed a method for the detection of Azacitidine at low concentrations using the differential pulse voltammetry (DPV). The peak current decreases in the oxidation signals of the deoxyguanosine obtained voltammetrically upon the interaction of Azacitidine and dsDNA allowed a sensitive determination of Azacitidine in pH 4.80 acetate buffer. A linear dependence of the deoxyguanosine oxidation signals was observed within the range of 2-20 µM Azacitidine, with a limit of detection (LOD) 0.62 µM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2023. Published by Elsevier B.V.)

Sucrose and high-fructose corn syrup comprise nearly equal amounts of glucose and fructose. With the use of high-fructose corn syrup in the food industry, consumption of fructose, which may be a tumor promoter, has increased dramatically. We examined fructose-induced oxidative DNA damage in the presence of Cu(II), with or without the addition of H 2 O 2 . With isolated DNA, fructose induced Cu(II)-mediated DNA damage, including formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), to a greater extent than did glucose, and H 2 O 2 enhanced the damage. In cultured human cells, 8-oxodG formation increased significantly following treatment with fructose and the H 2 O 2 -generating enzyme glucose oxidase. Fructose may play an important role in oxidative DNA damage, suggesting a possible mechanism for involvement of fructose in carcinogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The International Agency for Research on Cancer has classified arsenic as a class I carcinogen. Oxidative DNA damage is a typical early precursor to recognized malignancies. The most sensitive early independent marker of oxidative DNA damage is believed to be 8-hydroxy-2 deoxyguanosine (8-OHdG). To date, research on the link between urinary arsenic and 8-OHdG has not been consistent., Objective: This study was aimed at exploring the effects of urinary arsenic on 8-OHdG in human urine., Methods: A literature search until January 2023 was performed on the PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases through a combination of computer and manual retrieval. Stata 12.0 was used to examine the degree of heterogeneity among included studies. The percentage change and 95 % confidence interval (95 % CI) of 8-OHdG were calculated between populations exposed to different doses. We used a random effect model because the degree of heterogeneity exceeded 50 %. Sensitivity analysis and testing for publication bias were performed., Results: This meta-analysis included nine studies, most of which were performed in China. After exposure to arsenic, urinary arsenic (per 10 μg/g creatinine increase) was associated with the increased 8-OHdG (% change = 41.49 %, 95 % CI: 19.73 %, 63.25 %). Subgroup analysis indicated that the percentage change in 8-OHdG in urine was more pronounced in people exposed to arsenic <50 μg/L (% change = 24.60 %, 95 % CI: 17.35 %, 37.85 %). In studies using total urinary arsenic content as an indicator, the percentage change in 8-OHdG in urine was more significant (% change = 60.38 %, 95 % CI: 15.08 %, 105.68 %)., Conclusion: The 8-OHdG levels in human urine significantly increased after exposure to environmental arsenic, thus suggesting that arsenic exposure is correlated with oxidative DNA damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interest or personal relationship., (Copyright © 2023. Published by Elsevier B.V.)

Pancreatic cancer has a poor prognosis and is an important public health problem for developing countries. Oxidative stress plays an important role in cancer initiation, progression, proliferation, invasion, angiogenesis and metastasis. For this reason, one of the important strategic targets of new cancer therapeutics is to drive cancer cells into apoptosis through oxidative stress. In nuclear and mitochondrial DNA, 8-hydroxy-2′-deoxyguanosine and gamma-H2AX (γ-H2AX) are used as important oxidative stress biomarkers. Fusaric acid (FA) is a mycotoxin that mediates toxicity produced by Fusarium species and exhibits anticancer effects in various cancers via inducing apoptosis, cell cycle arrest, or other cellular mechanisms. The aim of this study was to determine the effects of fusaric acid on cytotoxic and oxidative damage in MIA PaCa-2 and PANC-1 cell lines. In this context, dose and time dependent cytotoxic effect of fusaric acid was determined by XTT method, mRNA expression levels of genes related to DNA repair were determined by RT-PCR, and its effect on 8-hydroxy-2′-deoxyguanosine and γ-H2AX levels was revealed by ELISA assay. According to XTT results, fusaric acid inhibits cell proliferation in MIA PaCa-2 and Panc-1 cells in a dose- and time-dependent manner. IC 50 doses were determined as 187.74 μM at 48 h in MIA PaCa-2 cells and 134.83 μM at 48 h in PANC-1 cells, respectively. γ-H2AX and 8-OHdG changes were not found significant in pancreatic cancer cells. The mRNA expression levels of DNA repair-related genes NEIL1, OGG1, XRCC and Apex-1 change with exposure to fusaric acid. This study contributes to the therapeutic approaches to be developed for pancreatic cancer and demonstrates the potential of fusaric acid as an anticancer agent. [Display omitted] • Fusaric acid decreases cell proliferation in PANC-1 and MiaPaca-2 pancreatic cancer cells. • The expression levels of DNA repair-related genes can be regulated by fusaric acid. • Fusaric acid increases 8-OHdG and gamma H2A X levels in pancreatic cancer cells. [ABSTRACT FROM AUTHOR]