Higher 8-OHdG Levels Research Articles

The Effect Of Pm2.5 Dust Exposure On Mda And 8-Ohdg Urine as an Oxidative Stress Indication Of Brick Workers in Mojokerto District, 2024

Exposure to PM2.5 dust could enter the human body through inhalation and have a negative impact on health through the mechanism of the formation of reactive oxygen species (ROS) in the respiratory tract, where the remaining ROS could burn cell nuclei and produce a byproduct in the form of malondialdehyde (MDA). In addition, oxygen radicals that could enter cells could burn DNA and produce 8-hydroxy-2'-deoxyguanosine (8-OHdG). High levels of MDA and 8-OHdG in the body reflect high levels of oxidative stress. Analyze sis influence on pap a ran PM 2.5 was an indication of oxidative stress through examination of urine MDA and 8-OHdG levels in brick-making workers in Mojokerto. Regency This type of research was observational and analytical, with a cross-sectional approach. There was an influence of exposure to PM 2.5 dust particles on MDA and 8-OHdG levels. MDA and 8-OHdG levels in the urine of workers at exposed locations were higher compared to workers at unexposed locations. The oxidative stress of workers in exposed locations was higher than that of workers in unexposed locations.

Multi-directional Changes in 8-OHdG Concentration in Saliva during HER2 Expression in Breast Cancer

The purpose of this work was to evaluate changes in the structure of 8-OHdG in saliva in patients with breast cancer depending on molecular biological subtypes. The findings show that decreased salivary 8-OHdG concentrations in the HER2-positive group rapidly correlated with decreased cell differentiation and high Ki-67 levels, reflecting the aggressive nature of the tumor disease and poor survival prognosis. Thus, the presence of high levels of 8-OHdG in the oral cavity may lead to the development of the role of a biological marker of the HER2-positive group with a poor prognosis of breast cancer and can be used as an additional method of diagnosis, patient condition and response to therapy.

Plasma 8-Hydroxy-2'-Deoxyguanosine, a Potential Valuable Biomarker for Atrial Fibrosis Is Influenced by Polymorphism of DNA Methylation Gene.

Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration. Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.

Association between atmospheric pollutant levels and oxidative stress in pregnant women and newborns in Urumqi

BackgroundFrequent 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.MethodsThis 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.ResultsA 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 < 0.001). The average values for AQI, PM2.5, PM10, SO2, NO2, and CO were higher in the heating season group (all P < 0.001). Maternal and neonatal PAHs were correlated with 8-OHdG measurements in maternal urine (r = 0.288, P < 0.001 and r = 0.336, P < 0.001) and neonatal umbilical cord blood (r = 0.296, P < 0.001 and r = 0.252, P < 0.001). There was also a positive relationship between PAHs, 8-OHdG levels in pregnant women and their newborns and proximate air pollutant concentrations (all P < 0.05). Based on the results of multiple linear regression analysis, it was found that air pollutants(PM10, 03) had a great influence on the level of 8-OHdG in neonatal cord blood, and the contribution rate was high(R2 = 0.320). Based on the epidemiological questionnaire, a multiple linear regression model was established(R2 = 0.496). We found that 8-OHdG levels in neonatal umbilical cord blood were mainly affected by two aspects: (1) Biological samples collected during heating had higher levels of 8-OHdG in neonatal umbilical cord blood. (2) Study may suggest that in neonates, males are more sensitive to oxidative damage.ConclusionParticulate air pollution may increase PAHs exposure and oxidative DNA damage in pregnant women and newborns.

Removal of lithium from aqueous solutions by solid-phase extraction using sawdust loaded with magnetite nanoparticles and study of apoptosis, MDA and 8-OHdG caused by lithium toxicity in fish brain.

Lithium, which has a high industrial value, is an environmental pollutant of concern to those who work with lithium in industry as well as to the general public. Biological parameters such as MDA, 8-OHdG, apoptosis (caspase-3), and acetylcholinesterase (AChE) were studied to determine the toxic effects on the brain tissue of the model organism (Carassius auratus) exposed to high dose lithium. According to the results obtained, it was found that lithium exposure caused oxidative stress with an increase in MDA level over time and, accordingly, DNA damage and apoptosis occured in brain tissue. It was also found that a decrease in AChE activity was observed, and the high levels of MDA, 8-OHdG, and caspase-3 activity obtained in brain tissue supported this result. The solid phase extraction (SPE) method was used to effectively remove lithium, which has unfavorable effects on living organisms, from aqueous solutions. In this method, a sawdust loaded with magnetite nanoparticles (MNLS) was prepared as an adsorbent for solid phase extraction by a simple method, and it was characterized. Optimal conditions for the SPE process were defined and it was found that lithium could be removed from solution onto the MNLS surface with a high yield of about 96%. The results of the study are crucial for proposing a simple and applicable high performance method.

Heat Exposure and Oxidative DNA Damage Among Bakery Workers in Duhok Province, Iraq

Background and rationales: There are not much researches on the effects of heat exposure, specifically on oxidative DNA damage, among bakery employees. Physical labor-intensive baking exposes bakers to high temperatures, especially in traditional bakeries with uncovered ovens. An electronic heat measuring device index and serum 8-hydroxy-2-deoxy guanosine(8-OHdG) will be utilized in this study to quantify oxidative DNA damage and heat stress, respectively. The impact of heat exposure on oxidative DNA damage in the Duhok populace has not yet been studied in the literature. This study aimed to measure the impact of heat exposure on serum levels of oxidative DNA damage in bakers who work in high-temperature bakeries. Method: A case control study was carried out among 141 participants, 62 individuals exposed to heat (bakery workers) and 79 individuals unexposed to heat exposure as control group. 8-hydroxy 2-deoxy guanosine (8-OHdG) has been analyzed using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The mean ±SD of 8-OHdG in bakery workers (13.78 ±5.89 ng/ml) were higher than those in healthy control individuals (1.55 ±0.75 ng/ml) with a statistically significantly differences (p&lt;0.0001). Conclusion: High mean levels of 8-OHdG was found in exposed individuals (bakery workers) in comparison with control individuals unexposed to heat, suggesting that high-heat exposures have the risk of causing genetic effects and DNA damage.

Usefulness of Urinary Biomarkers for Assessing Bladder Condition and Histopathology in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner’s lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner’s IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner’s IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology.

Oxidative Stress Markers in Cerebrospinal Fluid of Newly Diagnosed Multiple Sclerosis Patients and Their Link to Iron Deposition and Atrophy.

Oxidative stress has been implied in cellular injury even in the early phases of multiple sclerosis (MS). In this study, we quantified levels of biomarkers of oxidative stress and antioxidant capacity in cerebrospinal fluid (CSF) in newly diagnosed MS patients and their associations with brain atrophy and iron deposits in the brain tissue. Consecutive treatment-naive adult MS patients (n = 103) underwent brain MRI and CSF sampling. Healthy controls (HC, n = 99) had brain MRI. CSF controls (n = 45) consisted of patients with non-neuroinflammatory conditions. 3T MR included isotropic T1 weighted (MPRAGE) and gradient echo (GRE) images that were processed to quantitative susceptibility maps. The volume and magnetic susceptibility of deep gray matter (DGM) structures were calculated. The levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-iso prostaglandin F2α (8-isoPG), neutrophil gelatinase-associated lipocalin (NGAL), peroxiredoxin-2 (PRDX2), and malondialdehyde and hydroxyalkenals (MDA + HAE) were measured in CSF. Compared to controls, MS patients had lower volumes of thalamus, pulvinar, and putamen, higher susceptibility in caudate nucleus and globus pallidus, and higher levels of 8-OHdG, PRDX2, and MDA + HAE. In MS patients, the level of NGAL correlated negatively with volume and susceptibility in the dentate nucleus. The level of 8-OHdG correlated negatively with susceptibility in the caudate, putamen, and the red nucleus. The level of PRDX2 correlated negatively with the volume of the thalamus and both with volume and susceptibility of the dentate nucleus. From MRI parameters with significant differences between MS and HC groups, only caudate susceptibility and thalamic volume were significantly associated with CSF parameters. Our study shows that increased oxidative stress in CSF detected in newly diagnosed MS patients suggests its role in the pathogenesis of MS.

The Evaluation of Thiol/Disulfide Homeostasis and Oxidative DNA Damage in Patients with Obsessive Compulsive Disorder.

ObjectiveIn this study, we aimed to examine thiol/disulfide homeostasis and oxidative DNA damage in patients with OCD and compare them with healthy controls.MethodsThirty-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 μL 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.ResultsThe 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.ConclusionIncreased 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.

DNA damage, serum metabolomic alteration and carcinogenic risk associated with low-level air pollution

Outdoor air pollution has been classified as carcinogenic to humans (Group 1) for lung cancer, but the underlying mechanism and key toxic components remain incompletely understood. Since DNA damage and metabolite alterations are associated with cancer progression, exploring potential mechanisms linking air pollution and cancer might be meaningful. In this study, a real-time ambient air exposure system was established to simulate the real-world environment of adult male SD rats in Beijing from June 13th, 2018, to October 8th, 2018. 8-OHdG in the urine, γ-H2AX in the lungs and mtDNA copy number in the peripheral blood were analyzed to explore DNA damage at different levels. Serum non-targeted metabolomics analysis was performed. Pair-wise spearman was used to explore the correlation between DNA damage biomarkers and serum differential metabolites. Carcinogenic risks of heavy metals and PAHs via inhalation were assessed according to US EPA guidelines. Results showed that PM2.5 and O3 were the major air pollutants in the exposure group and not detected in the control group. Compared with control group, higher levels of 8-OHdG, mtDNA copy number, γ-H2AX and PCNA-positive nuclei cells were observed in the exposure group. Histopathological evaluation suggested ambient air induced alveolar wall thickening and inflammatory cell infiltration in lungs. Perturbed metabolic pathways identified included glycolysis/gluconeogenesis metabolism, purine and pyrimidine metabolism, etc. γ-H2AX was positively correlated with serum ADP, 3-phospho-D-glyceroyl phosphate and N-acetyl-D-glucosamine. The BaPeq was 0.120 ng/m3. Risks of Cr(VI), As, V, BaP, BaA and BbF were above 1 × 10−6. We concluded that low-level air pollution was associated with DNA damage and serum metabolomic alterations in rats. Cr(VI) and BaP were identified as key carcinogenic components in PM2.5. Our results provided experimental evidence for hazard identification and risk assessment of low-level air pollution.

In-vitro STUDY OF ACRYLAMIDE AND TBHQ COMPOUNDS ON THE GENERATION OF DNA ADDUCT 8-HYDROXY-2’- DEOXYGUANOSINE AS BIOMARKER OF OXIDATIVE DNA DAMAGE

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.

Proinflammatory and Oxidative Stress States Induced by Human Papillomavirus and Chlamydia trachomatis Coinfection Affect Sperm Quality in Asymptomatic Infertile Men.

Background and Objectives: To investigate the effect of infection with human papillomavirus (HPV) or Chlamydia trachomatis (CT) and HPV + CT coinfection on sperm quality, inflammation, and the state of oxidative stress (OS) in asymptomatic infertile men. Materials and Methods: Semen samples from 84 asymptomatic military infertile men were studied. The polymerase chain reaction (PCR) was used for the molecular detection of HPV and CT. Semen parameters were analyzed according to the World Health Organization guidelines. Inflammation was evaluated by an IL-1β, IL-6, and IFN-γ enzyme-linked immunosorbent assay (ELISA) and OS by the quantification of lipid peroxidation (LPO), 8-hydroxydeoxyguanosine (8-OHdG), and total antioxidant capacity (TAC). Results: A total of 81 of the 84 (96.4%) samples were positives for the pathogens, with 55/81 (68%) being positive for HPV, 11/81 (13.5%) for CT, and 15/81 (18.5%) for HPV + CT coinfection. Seminal parameters were affected in the infected groups, including pH increases above the normal range in all groups. An abnormal sperm morphology was observed in the HPV and HPV + CT groups. Higher cytokine levels were detected in the HPV group and the highest IL-1β level was found in the HPV + CT group. No cytokines were detected in the CT group. High LPO and 8-OHdG levels were found in all groups with a lower TAC. Comparisons between groups showed the highest OS state was observed in the HPV group. Conclusions: High HPV infection or coinfection (HVP + CT) in these infertile men suggest compromising male fertility by inducing a proinflammatory state and OS. Infection with CT suggests an alteration of the state of OS by promoting an alkaline pH.

The Adverse Effect of Air Pollution with Polycyclic Aromatic hydrocarbon (PAH) on 8-OXO-DG and gene expression (HOGG1) in Midland Refineries Company-Daura Refinery Workers

Introduction: Polycyclic aromatic hydrocarbons (PAHs) are a group of different kind of hazardous organic chemicals which are considered to be the top of pollutants that released by petroleum industries exploration activities to the environment. PAH Metabolites that affect initiation of cancer by reaction with DNA are practically modified chemically by enzymes. PAH Mutagenic metabolites include radical PAH cations, diol epoxides, and quinones. Reactive oxygen species (ROS) mostly produce by routine oxidation processes in mitochondria is responsible for many types of DNA damage. The aim of study identify the DNA alteration due to air pollution by modulation of gene expression and regulatory gene Human 8-oxoguanine DNA Glycosylase (HOOG1) and association with 7,8-dihydro-8-oxoguanine (8-oxo-dg). Methods: there were 168 participants included in this study divided in three groups (control, office workers and in field workers) .PAH, 8-OXO-DG and gene expression (HOGG1) detected for each participant by GC/MS, competitive ELISA and quantitative-competitive reverse transcription-PCR respectively. Results: PAH were not detected in the blood of control group, and there was significant difference in the concentration of PAH between office and field workers. The concentration of (8-oxo DG) and (hOGG1) was significantly higher in field worker than in office worker and control group, significant difference was found between office workers and control. Discussion: It is observed that increased levels of PAH and its metabolites when exposed to polluted air. PAHs metabolism is associated with production of ROS as well as oxidative damaged. Among this damage, the most common lesion is (8-OHdG) .Increase in (8-OHdG) levels associated with increase oxidative stress and (HOGG1) gene. Conclusion: (a) increased PAH and its metabolites levels in serum causing high 8-OHdG and (HOGG1) expression levels in refineries workers (b) there is a correlation between 8-OHdG and hOGG1 expression with PAH.

Effects of Sodium Glucose Cotransporter 2 Inhibitor on Renal Renin-Angiotensin-Aldsoterone System

Objective: The renoprotective effect of sodium glucose cotransporter 2 inhibitor (SGL2i) has been reported in diabetic patients. Local renin-angiotensin-aldosterone system (RAAS) is activated in diabetes mellitus and hypertension. We examined the effects of SGL2i on the RAAS in the obese diabetic rats fed a high salt diet. Methods: Zucker-diabetic rats (ZDR) and control rats were fed a high or normal salt diet and were treated with canagliflozin for 8 weeks. Blood pressure (BP), blood glucose (BG), PRA, plasma aldosterone (PAC), urinary albumin excretion (UAE), urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), gene expression of angiotensinogen in the kidney were measured. Results: ZDR febd a high salt diet showed high BP, increased UAE and urinary 8-OHdG and elevated angiotensinogen mRNA levels. Treatment with canagliflozin significantly decreased BP, BG, UAE, urinary 8-OHdG and and renal angiotensinogen mRNA levels compared with control rats (p<0.05). Discussion and Conclusion: The closer mechanism of renoptotection of SGL2i in diabetes mellitus is unclear. We have reported that the repoprotective effects of type 2 angiotensin receptor antagonist or mineralocorticoid receptor blocker were partly due to the decreased RAAS in the kidney. Decreased renal RAAS by the treatment with canagliflozin may contribute to the renoprotection in DZR.

A study of oxidative stress in cervical cancer- an institutional study

Cervical cancer is the second most common cause of cancer-related death among women worldwide, especially in developing countries. Oxidative stress has been associated with cervical cancer. Many studies demonstrated that the low level of antioxidants induces the production of free radicals that cause lipid peroxidation, DNA, and protein damage leading to mutations that favors malignant transformation. This is a case-control institutional study conducted to evaluate the level of oxidative stress in cervical cancer patients and the age-matched healthy controls. We measured level of TBARS expressed as MDA, activity of SOD and GSH level by the spectrophotometric method, and level of 8-OHdG was estimated using a competitive sandwich ELISA assay. Our results showed a significant increase in the level of lipid peroxidation in group IV when compared to the control, group II and group III (p < 0.001). The activity of SOD was also significantly higher in group IV when compared to the control group (p < 0.001), group II (p < 0.001), and group III (p < 0.001). The level of GSH was also significantly lower in group IV when compared to the control group (p < 0.01), group II (p < 0.01), and group III (p < 0.01). The level of 8-OHdG was significantly higher in group IV than in the other groups (p < 0.01). The results suggest that oxidative stress is involved in the pathogenesis of cervical cancer, which is demonstrated by an increased level of lipid peroxidation and higher levels of 8-OHdG and an altered antioxidant defense system.

Abstract 4617: Association between DNA oxidative damage and radiotherapy-induced skin toxicities in breast cancer patients

Abstract Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death in the female population in the United States. Although radiotherapy (RT) has been shown to improve prognosis in breast cancer patients, RT may also lead to side effects that impact overall quality of life in some patients. The objective of this study was to investigate whether an oxidative damage biomarker, 8-hydroxy-2-deoxyguanosine (8-OHdG), is associated with RT-induced early adverse skin reactions (EASRs) in breast cancer patients. Methods: 8-OHdG data before (pre-RT) and after RT (post-RT) were obtained from 475 breast cancer patients. RT-induced EASRs were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (v3.0) scale. Univariate logistic regression analyses were conducted to evaluate associations between above-median 8-OHdG (&amp;gt; 85 ng/ml) and RT-induced grade 2+ EASRs. A propensity score (PS) was derived from a logistic regression model for predicting RT-induced EASRs on the basis of patient, tumor, and treatment characteristics. Then, the association between 8-OHdG and RT-induced EASRs was assessed in four risk groups defined by quartiles of PS. Results: Overall, 59% of patients developed RT-induced grade 2+ EASRs and 28% developed moist desquamation. There were no significant associations between RT-induced EASRs and high 8-OHdG levels at both pre-RT and post-RT. However, there was a significant association between patients in the 2nd quartile PS that had high post-RT 8-OHdG levels and grade 2+ EASRs (OR=2.51, 95%CI=1.17, 5.40, p=0.0183). Conclusions: The results from this study suggest that 8-OHdG is a potential biomarker for RT-induced EASRs in a breast cancer population with low to medium (2nd quartile) propensity for RT-induced EASRs. Citation Format: Moody M. Mihyu, Isildinha M. Reis, Cristiane Takita, Jean L. Wright, Eunkyung Lee, Omar L. Nelson, George R. Yang, Johnna L. Bakalar, Jennifer J. Hu. Association between DNA oxidative damage and radiotherapy-induced skin toxicities in breast cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4617.

Relationships among cigarette smoking, urinary biomarkers, and urothelial carcinoma risk: a case-control study.

Cigarette smoke is a known risk factor for urothelial carcinoma (UC). However, there is limited information about the distributions and effects of volatile organic compounds (VOCs) on smoking-related UC risk. With this hospital-based case-control study, we explored the associations between urinary levels of cotinine and VOC metabolites (acrylamide, 1,3-butadiene, and benzene) and the risk of UC. Urological examinations and pathological verifications were used to confirm the diagnoses of UC. All study participants provided smoking-related information via questionnaires and face-to-face interviews; they also provided urine samples for the measurement of VOC metabolites, cotinine, and 8-hydroxydeoxyguanosine (8-OHdG), which was used as an indicator of oxidative stress. We applied multiple logistic regression analysis to estimate the risk of UC, and we found that levels of urinary cotinine and 8-OHdG were higher in the UC group than in the control group. Furthermore, urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine-3, trans,trans-muconic acid (t,t-MA), and S-phenylmercapturic acid (SPMA), increased with increasing levels of urinary cotinine. After adjusting for potential risk factors, dose-response relationships were observed between UC risk and urinary levels of AAMA, t,t-MA, SPMA, and 8-OHdG. Participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG had risks of UC that were 3.5- to 6-fold higher than those of participants with lower levels. Future, large-scale investigations of the risks of UC should be explored, and repeated measurement of VOC metabolites should be assessed.

Clinical impact of admission urinary 8-hydroxydeoxyguanosine level for predicting cardiovascular mortality in patients with acute coronary syndrome.

The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.92ng/mg creatinine; and a low admission urinary 8-OHdG group, 382 patients with admission urinary 8-OHdG < 17.92ng/mg creatinine. The patients were followed up for a median period of 34months. The primary and secondary end points were the incidence of cardiovascular death and major cardiovascular events (MACE) composed of cardiovascular death, non-fatal myocardial infarction, or urgent hospitalization for heart failure. Of the 551 patients, cardiovascular deaths and MACE occurred in 14 (2.5%) and 35 (6.4%), respectively. The Kaplan-Meier estimate of the event-free rate revealed cardiovascular deaths and MACE were more likely in the high admission 8-OHdG group than in the low admission 8-OHdG group (log rank, both P < 0.001). Multiple adjusted Cox proportional hazards analysis indicated that high admission urinary 8-OHdG was an independent predictor of cardiovascular death (hazard ratio [HR] 7.642, P = 0.011) and MACE (HR 2.153, P = 0.049). High admission urinary 8-OHdG levels predict cardiovascular mortality after adjustment in patients with ACS.

Detection of DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a toxicity bioindicator to the effects of nickel on Ni-Cr alloy prosthesis users.

Previous studies have suggested that exposure to Ni from Ni-Cr alloys can affect the human body through oxidative stress. The present study discusses the effect of nickel from Ni-Cr alloy prostheses on the formation of DNA Adduct 8-Hydroxy-2′-Deoxyguanosine (8-OHdG), evaluated based on creatinine and 8-OHdG concentrations in urine, determined with LC-MS/MS, for a Ni-Cr alloy user group and a never-user control group. The mean creatinine and 8-OHdG concentrations were not significantly different between the test groups, although highest levels were observed for the in the Ni-Cr user group. It is suggested that samples with relatively high creatinine and/or 8-OHdG levels are further studied in more detail for stability of concentrations and for the effect of contributing factors.

Urinary 8-Hydroxy-2'-Deoxyguanosine Levels and Cardiovascular Disease Incidence in Japan.

Aim: The association between urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative stress marker, and the incidence of cardiovascular disease (CVD) has not been confirmed because no previous studies evaluated 24-hour 8-OHdG excretion levels in the general population. We aimed to confirm the association between 24-hour urinary 8-OHdG levels and CVD risk among Japanese men and women.Methods: A nested case-control study was performed based on a 24-hour urine collection in a community-based cohort study performed from 1996 to 2005. Seventy-six cases (55 men and 21 women) who experienced their first CVD incidence during the follow-up period (median: 5.9 years) were recruited. The controls were frequency-matched 1:2, with each case for sex, age, area of residence, and baseline year. The 8-OHdG level was measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for body mass index, ethanol intake, smoking status, and estimated glomerular filtration rate.Results: The geometric mean and geometric standard deviation (SD) of 8-OHdG levels (nmol/day) for cases and controls were 35.5 (1.55) and 35.5 (1.54) for men and 32.1 (1.35) and 25.0 (1.39) for women, respectively. The multivariable OR (95% CI) of CVD incidence according to the 1-SD increment of the log-transformed 8-OHdG level was 2.08 (0.99–4.37) for women. The multivariable ORs (95% CIs) for the 1st (lowest) and 4th versus 2nd quartile according to 8-OHdG for men were 3.29 (1.02–10.61) and 2.77 (0.96–7.96), respectively.Conclusion: A high 8-OHdG level tended to be associated with CVD incidence among women.