Differences In DNA Damage Research Articles

Are patients with severe obesity aging faster? Impact of severe obesity on different aspects of biological age.

Obesity and aging are characterized by chronic low‑grade inflammation, which contributes to the onset of degenerative processes. Our objective was to comprehensively analyze the prevalence of premature aging in patients with obesity and identify metabolic factors influencing aging. In this prospective cohort study, telomere length, DNA damage, interleukin 6 (IL‑6) level, metabolic age, and cognitive functions were evaluated in patients with severe obesity (study group [SG], defined as body mass index [BMI] equal to or above 40 kg/m2 or equal to or above 35 kg/m2 with comorbidities; n = 100) and healthy volunteers (control group [CG], defined as BMI 18.5-24.9 kg/m2; n = 33). The SG was further divided into 2 subgroups, SG1 comprising patients with BMI equal to or above 50 kg/m2 and SG2 with BMI below 50 kg/m2. Our findings showed that individuals in the SG had shorter telomeres, higher levels of inflammation, and more advanced metabolic age than those in the CG. However, no significant differences in DNA damage or cognitive function abilities were observed between the groups. Notably, the SG1 displayed elevated IL‑6 levels as compared with the SG2. Furthermore, IL‑6 levels decreased significantly with increasing body fat, and the individuals with higher visceral fat levels had longer telomeres. Premature aging manifests in obesity through telomere length, inflammation levels, and metabolic age. Aging in obesity should be considered as a nonlinear process.

High and low performing sires differ in their contributions to early embryonic stress in the bovine.

Context Sires differ in their ability to produce viable blastocysts, yet our understanding of the cellular mechanisms regulated by the sire during early embryo development is limited. Aims The first aim was to characterise autophagy and reactive oxygen species (ROS) in embryos produced by high and low performing sires under normal and stress culture conditions. The second aim was to evaluate DNA damage and lipid peroxidation as mechanisms that may be impacted by increased cellular stress, specifically oxidative stress. Methods Embryos were produced using four high and four low performing sires based on their ability to produce embryos. Autophagy and ROS were measured throughout development. To evaluate oxidative stress response, autophagy, and ROS were measured in 2-6 cell embryos exposed to heat stress. To understand how cellular stress impacts development, DNA damage and lipid peroxidation were assessed. Key results Under normal conditions, embryos from low performing sires had increased ROS and autophagy. Under heat stress, embryos from low performing sires had increased ROS, yet those from high performing sires had increased autophagy. There was no difference in DNA damage or lipid peroxidation. Conclusions Results suggest that embryos from low performing sires may begin development under increased cellular stress, and autophagy potentially increases to mitigate the impacts of stress. Implications There is potential for improving embryonic competence through selection of sires with lower stress-related markers.

Exploring the relationship between genetic instability and health outcomes in acute and chronic post-COVID syndrome.

The COVID-19 pandemic has led to the emergence of acute and chronic post-COVID syndromes, which present diverse clinical manifestations. The underlying pathophysiology of these conditions is not yet fully understood, but genetic instability has been proposed as a potential contributing factor. This study aimed to explore the differential impact of physical and psychological health factors on genetic instability in individuals with acute and chronic post-COVID syndromes. In this study, three groups of subjects were analyzed: a control group, an acute post-COVID group, and a chronic post-COVID group, with a total of 231 participants. The participants were assessed using a questionnaire for long-COVID-19COVID, and female participants reported more symptoms than male participants in areas related to fatigue, memory, mental health, and well-being during the chronic phase. Genetic instability was assessed using the comet assay, and participants' physical and psychological profiles were evaluated. The overall results showed no significant differences in DNA damage, as measured by the comet assay, among the three groups, suggesting that genetic instability, as assessed by this method, may not be a primary driver of the distinct clinical presentations observed in post-COVID syndromes. However, when gender was considered, male participants in the acute long COVID group exhibited higher levels of genetic instability compared to females. Multiple linear regression analysis revealed that gender, age, and waist circumference were significant predictors of DNA damage. Among females in the acute group, sexual health, and eye-related symptoms significantly influenced the increase in DNA damage. These findings indicate the need for further investigation on the gender-specific differences in genetic instability and their potential implications for the pathophysiology of post-COVID syndromes. Exploring alternative markers of genetic instability and the interplay between genetic, inflammatory, and cellular processes could provide valuable insights for the management of these debilitating post-viral sequelae.

Comparison of mutation spectra induced by gamma-rays and carbon ion beams.

The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and X-rays. This indicates a difference in the DNA damage produced by low and high LET radiations and their biological effects. We have been studying the differences in DNA damage produced by gamma-rays and carbon ion beams. Therefore, we analyze mutations induced by both ionizing radiations to discuss the differences in their biological effects in this study. pUC19 plasmid DNA was irradiated by carbon ion beams in the solution containing 1M dimethyl sulfoxide to mimic a cellular condition. The irradiated DNA was cloned in competent cells of Escherichia coli. The clones harboring some mutations in the region of lacZα were selected, and the sequence alterations were analyzed. A one-deletion mutation is significant in the carbon-irradiated DNA, and the C:G↔T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C↔T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations.

Systemic DNA Damage and Repair Activity Vary by Race in Breast Cancer Survivors.

Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the target tissue (e.g., breast). We investigated race-based differences in DNA damage and repair, using a novel CometChip assay, in circulating leukocytes from breast cancer survivors who had completed primary cancer therapy and were cancer free. We observed novel race-based differences in systemic DNA damage and repair activity in cancer survivors, but not in cells from healthy volunteers. Basal DNA damage in leukocytes was higher in White survivors, but Black survivors showed a much higher induction after bleomycin treatment. Double-strand break repair activity was also significantly different between the races, with cells from White survivors showing more sustained repair activity compared to Black leukocytes. These results suggest that cancer and cancer therapy might have long-lasting effects on systemic DNA damage and repair mechanisms that differ in White survivors and Black survivors. Findings from our preliminary study in non-cancer cells (circulating leukocytes) suggest systemic effects beyond the target site, with implications for accelerated aging-related cancer survivorship disparities.

Radiation-induced DNA double-strand breaks in cortisol exposed fibroblasts as quantified with the novel foci-integrated damage complexity score (FIDCS)

Without the protective shielding of Earth’s atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chronic cortisol exposure during spaceflight raises further concerns, although its specific impact on DNA damage and repair remains unknown. This study explorers the effect of different radiation qualities (photons, protons, carbon, and iron ions) on the DNA damage and repair of cortisol-conditioned primary human dermal fibroblasts. Besides, we introduce a new measure, the Foci-Integrated Damage Complexity Score (FIDCS), to assess DNA damage complexity by analyzing focus area and fluorescent intensity. Our results show that the FIDCS captured the DNA damage induced by different radiation qualities better than counting the number of foci, as traditionally done. Besides, using this measure, we were able to identify differences in DNA damage between cortisol-exposed cells and controls. This suggests that, besides measuring the total number of foci, considering the complexity of the DNA damage by means of the FIDCS can provide additional and, in our case, improved information when comparing different radiation qualities.

Gender Difference in DNA Damage Induced by the Environmental Carcinogen Dibenzo[def,p]chrysene Individually and in Combination with Mouse Papillomavirus Infection in the Mouse Oral Cavity.

Tobacco smoking and human papillomavirus infection are established etiological agents in the development of head and neck squamous cell carcinoma (HNSCC). The incidence and mortality of HNSCC are higher in men than women. To provide biochemical basis for sex differences, we tested the hypothesis that carcinogen treatment using dibenzo[def,p]chrysene, which is an environmental pollutant and tobacco smoke constituent, in the absence or presence of the mouse papillomavirus infection results in significantly higher levels of DNA damage in the oral cavity in male than in female mice. However, the results of the present investigation do not support our hypothesis since we found that females were more susceptible to carcinogen-induced covalent DNA damage than males independent of the viral infection. Since DNA damage represents only a single-step in the carcinogenesis process, additional factors may contribute to sex differences in humans.

Exploration of the tumorigenic, metabolic, and cognitive consequences of tau protein removal

AbstractBackgroundTau accumulation causes tauopathies and drives cellular senescence, which can lead to inflammation, neurodegeneration, and cognitive impairment. The association between intracellular tau deposition and pathogenesis has prompted therapeutic strategies that reduce tau expression. However, tau is also critical in microtubule stabilization, synaptic plasticity, and maintaining DNA integrity. We investigated the impact of tau removal on brain cell senescence and associated neurocognitive behaviors in aged tau knockout (Mapt0/0) and wild type control (Mapt+/+) mice. We also assessed physical, metabolic, histological, and biochemical outcomes in Mapt0/0 and Mapt+/+ mice and in response to high fat diet (HFD), a stressor that drives DNA damage.Method20‐month‐old female Mapt0/0 and Mapt+/+ mice were subjected to the Elevated Plus Maze to assess anxiety‐like behavior. Mice were then fed control (CTL) or HFD (60% kcal fat) for 9 weeks. Behavioral and physical measures were then assessed, and brain tissue was further analyzed via gene expression, biochemistry, and histological assays.ResultTau knockout and HFD, separately and additively, caused weight gain and insulin resistance. Removing tau primed cells to proliferate, as Mapt0/0 mice had increased body size, organ size, and tumor burden compared to Mapt+/+. We observed no difference in senescence between genotypes on CTL diet. The HFD increased senescence only in Mapt+/+ mice, whereas Mapt0/0 mice displayed increased tumor burden. Mapt0/0 mice displayed anxiety‐ and depressive‐like behaviors on both diets. Transcriptomic and protein expression data revealed that several molecules responded similarly to tau removal and HFD exposure, but Mapt+/+ and Mapt0/0 mice responded differently to HFD. Genotype differences in DNA damage and cell cycle dysregulation were also observed.ConclusionMapt0/0 mice did not accumulate senescent cells but demonstrated anxiety‐like behaviors in the presence of elevated DNA damage; thus tau knockout may drive neuropsychiatric phenotypes which can be dissociated from obesity and senescence. Mapt0/0 mice also developed tumors, suggesting that tau plays a critical role in cell fate decisions, including senescence versus cancer. Overall, we found that tau removal prevents senescent cell accumulation with the tradeoff of tumorigenic, metabolic, and cognitive consequences. We caution against removing tau until a better understanding of its physiological roles are defined.

γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids.

Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies. In addition to αβ T cells and natural killer (NK) cells, γδ T cells represent an immune cell population with significant therapeutic potential against both hematologic and solid tumours. To evaluate the efficacy of γδ T cells in cervical cancer treatment, we generated patient-derived healthy and cancer ectocervical organoids. Furthermore, we examined transformed healthy organoids, expressing HPV16 oncogenes E6 and E7. We analysed the effector function of in vitro expanded γδ T cells upon co-culture with organoids. Our findings demonstrated that healthy cervical organoids were less susceptible to γδ T cell-mediated cytotoxicity compared to HPV-transformed organoids and cancerous organoids. To identify the underlying pathways involved in this observed cytotoxicity, we performed bulk-RNA sequencing on the organoid lines, revealing differences in DNA-damage and cell cycle checkpoint pathways, as well as transcription of potential γδ T cell ligands. We validated these results using immunoblotting and flow cytometry. We also demonstrated the involvement of BTN3A1 and BTN2A1, crucial molecules for γδ T cell activation, as well as differential expression of PDL1/CD274 in cancer, E6/E7+ and healthy organoids. Interestingly, we observed a significant reduction in cytotoxicity upon blocking MSH2, a protein involved in DNA mismatch-repair. In summary, we established a co-culture system of γδ T cells with cervical cancer organoids, providing a novel in vitro model to optimize innovative patient-specific immunotherapies for cervical cancer.

Comparing P53 expression and genome-wide transcriptome profiling to Comet assay in lymphocytes from melanoma patients and healthy controls.

This study compared the expression of TP53 in lymphocytes from malignant melanoma (MM) patients with positive sentinel nodes to healthy controls (HCs) following exposure to various doses of UVA radiation. The Lymphocyte Genome Sensitivity (LGS) assay indicated significant differences in DNA damage in lymphocytes between MM patients and HCs. qPCR data demonstrated an overall 3.4-fold increase in TP53 expression in lymphocytes from MM patients compared to healthy controls, following treatment with 0.5 mW/cm2 UVA radiation. Western blotting confirmed that p53 expression was increased in MM lymphocytes following UVA exposure compared to healthy individuals. Genome transcriptome profiling data displayed differences in gene expression between UVA-treated lymphocytes from MM patients and HCs. Peripheral lymphocytes from MM patients are more susceptible to the genotoxic effects of UVA compared to healthy individuals. Our previous studies showed that UVA exposure of various intensities caused significant differences in the levels of DNA damage between lymphocytes from cancer patients compared to HCs through the LGS assay. The present study's results provide further credibility to the LGS assay as a screening test for cancer detection. Peripheral lymphocytes could be a promising blood biopsy biomarker for staging of carcinomas and prevention of carcinoma progression at early stages.

Bioenergetic function is decreased in peripheral blood mononuclear cells of veterans with Gulf War Illness.

Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial dysfunction is an important contributor to GWI, based on the similarity of some GWI symptoms to those occurring in some mitochondrial diseases; the plausibility that certain pollutants to which GW veterans were exposed affect mitochondria; mitochondrial effects observed in studies in laboratory models of GWI; and previous evidence of mitochondrial outcomes in studies in GW veterans. A primary role of mitochondria is generation of energy via oxidative phosphorylation. However, direct assessment of mitochondrial respiration, reflecting oxidative phosphorylation, has not been carried out in veterans with GWI. In this case-control observational study, we tested multiple measures of mitochondrial function and integrity in a cohort of 114 GW veterans, 80 with and 34 without GWI as assessed by the Kansas definition. In circulating white blood cells, we analyzed multiple measures of mitochondrial respiration and extracellular acidification, a proxy for non-aerobic energy generation; mitochondrial DNA (mtDNA) copy number; mtDNA damage; and nuclear DNA damage. We also collected detailed survey data on demographics; deployment; self-reported exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents; and current biometrics, health and activity levels. We observed a 9% increase in mtDNA content in blood in veterans with GWI, but did not detect differences in DNA damage. Basal and ATP-linked oxygen consumption were respectively 42% and 47% higher in veterans without GWI, after adjustment for mtDNA amount. We did not find evidence for a compensatory increase in anaerobic energy generation: extracellular acidification was also lower in GWI (12% lower at baseline). A subset of 27 and 26 veterans returned for second and third visits, allowing us to measure stability of mitochondrial parameters over time. mtDNA CN, mtDNA damage, ATP-linked OCR, and spare respiratory capacity were moderately replicable over time, with intraclass correlation coefficients of 0.43, 0.44, 0.50, and 0.57, respectively. Other measures showed higher visit-to-visit variability. Many measurements showed lower replicability over time among veterans with GWI compared to veterans without GWI. Finally, we found a strong association between recalled exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents and GWI (p < 0.01, p < 0.01, and p < 0.0001, respectively). Our results demonstrate decreased mitochondrial respiratory function as well as decreased glycolytic activity, both of which are consistent with decreased energy availability, in peripheral blood mononuclear cells in veterans with GWI.

Genotoxic, mutagenic, and cytotoxic analysis in bats in mining area.

Pollution generated by the mining industry can cause harm to wildlife. This study aimed to evaluate the cytotoxicity, genotoxicity and mutagenicity in bats environmentally exposed to open pit mining. Thus, 62 bats of the following species, Carollia perspicillata, Glossophaga soricina, Phyllostomus hastatus, and Desmodus rotundus exposed to mining activities (ferronickel) were used in the analysis. The animals were obtained in samplings in July and November of 2021, totaling 8days of sampling in the field. The results indicated that species differ in the frequency of genotoxic damage between sampling points within the mining landscape. Cytotoxicity was observed by scoring of karyorrhexis, pyknosis and karyolysis. The most captured species, C. perspicillata, showed differences in DNA damage between exposed and unexposed populations, but no differences were observed between males (n = 14) and females (n = 20). G. soricina was also a sensitive species for indicating a high frequency of DNA damages compared to the omnivore P. hastatus. Elements such as Mn, Cr, Pb, and Zn observed in water samples were at high levels in the mining area. We conclude that bats in mining areas are susceptible to increased DNA damage as already identified for other species.

Investigation Of Genotoxic Effect Of Octyl Gallate Used As An Antioxidant Food Additive In In Vitro Test Systems.

Several antioxidant food additives are added to oils, soups, sauces, chewing gum, potato chips etc. One of them is octyl gallate. The purpose of this study was to evaluate the potential genotoxicity of octyl gallate in human lymphocytes, using in vitro chromosomal abnormalities (CA), sister chromatid exchange (SCE), cytokinesis block micronucleus cytome (CBMN-Cyt), micronucleus-FISH (MN-FISH), and comet tests. Different concentrations (0.50, 0.25, 0.125, 0.063, and 0.031 μg/mL) of octyl gallate were used. A negative (distilled water), a positive (0.20 μg/mL Mitomycin-C), and a solvent control (8.77 μL/mL ethanol) were also applied for each treatment. Octyl gallate did not cause changes in chromosomal abnormalities, micronucleus, nuclear bud (NBUD) and nucleoplasmic bridge (NPB) frequency. Similarly, there was no significant difference in DNA damage (comet assay), percentage of centromere positive and negative cells (MN-FISH test) compared to the solvent control. Moreover, octyl gallate did not affect replication and nuclear division index. On the other hand, it significantly increased the SCE/cell ratio in three highest concentrations compared to solvent control at 24h treatment. Similarly, at 48h treatment, the frequency of SCE raised significantly compared to solvent controls at all the concentrations (except 0.031 μg/mL). An important reduce was detected in mitotic index values in highest concentration at 24h treatment and almost all concentrations (except 0.031 and 0.063 µg / mL) at 48h treatment. The results obtained suggest that octyl gallate has no an important genotoxicological action on human peripheral lymphocytes at the concentrations applied in this study.

Varied Photon Radiation Sources Produce Differences in Cellular Response.

In vitro studies allow evaluation of normal or cancer cell responses to radiation, either alone or in combination with agents used to modify these biological responses. Ionizing radiation can be produced by a variety of particles and sources, with varying energy spectra, interaction probabilities, linear energy transfer, dose uniformity, dose rates, and delivery methods. Multiple radiation sources have been used to irradiate cells in the published literature. However, the equivalence of response in cell culture models across radiation sources has not been rigorously established. Moreover, current reporting of radiation source parameters lacks consistency and rigor which may impact the reproducibility of pre-clinical data between laboratories. Relevant choices of radiation source are also of high importance due to growing interest in comparing photon versus particle radiation effect on biological responses. Therefore, this study robustly evaluates the cellular response (cell survival, apoptosis, and DNA damage) of three distinct cell lines using four unique photon generating radiation sources. We hypothesize there may be subtle differences across the radiation sources, without an appreciable difference in cellular response. The four photon irradiation energies investigated, 662 keV, 100 kVp, 220 kVp, 6 MV, did produce subtle differences in DNA damage and cell survival when treating three distinct tumor cell lines. These variations in cellular response emphasize the need to carefully consider irradiation source, energy, and dose rate depending on study goal and endpoint.

Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection.

Acute type A aortic dissection (AAD) is a catastrophic disease with high mortality, but the pathogenesis has not been fully elucidated. This study is aimed at identifying hub genes and immune cells associated with the pathogenesis of AAD. The datasets were downloaded from Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA), gene set variation analysis (GSVA), and differential analysis were performed. The differentially expressed genes (DEGs) were intersected with specific genes collected from MSigDB. The gene function and pathway enrichment analysis were also performed on intersecting genes. The key modules were selected by weighted gene coexpression network analysis (WGCNA). Hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis and were verified in the metadataset. The immune cell infiltration was analyzed by CIBERSORT, and the relationship between hub genes and immune cells was performed by Pearson's correlation analysis. The single-cell RNA sequencing (scRNA-seq) dataset was used to verify the differences in DNA damage and repair signaling pathways and hub genes in different cell types. The results of GSEA and GSVA indicated that DNA damage and repair processes were activated in the occurrence of AAD. The gene function and pathway enrichment analysis on differentially expressed DNA damage- and repair-related genes showed that these genes were mainly involved in the regulation of the cell cycle process, cellular response to DNA damage stimulus, response to wounding, p53 signaling pathway, and cellular senescence. Three key modules were identified by WGCNA. Five genes were screened as hub genes, including CDK2, EIF4A1, GLRX, NNMT, and SLCO2A1. Naive B cells and Gamma delta T cells (γδ T cells) were decreased in AAD, but monocytes and M0 macrophages were increased. scRNA-seq analysis included that DNA damage and repair processes were activated in smooth muscle cells (SMCs), tissue stem cells, and monocytes in the aortic wall of patients with AAD. Our results suggested that DNA damage- and repair-related genes may be involved in the occurrence of AAD by regulating many biological processes. The hub genes and immune cells reported in this study also increase the understanding of AAD.

Iron supplementation does not aggravate impaired glucose tolerance and sugar overload-induced genotoxicity in rats.

High sugar intake is a major risk factor for metabolic disorders. Genotoxicity is an important factor in diabetes onset, and iron (Fe) may be an aggravating element. However, this relationship is still poorly established. Thus, this study evaluated whether Fe supplementation could aggravate obesity, impaired glucose tolerance, and sugar overload-induced genotoxicity in rats. A total of 24 rats were treated with different diets: standard diet (SD, n = 8), invert sugar overload (320g/L, HSD, n = 8), or Fe plus invert sugar overload (2.56mg/L of Fe2+, Fe-HSD, n = 8) for four months. After treatment, the Fe-HSD group showed no excessive weight gain or impaired glucose tolerance. DNA damage in blood, as assessed by comet assay, gradually increased in HSD during treatment (p < 0.001), whereas Fe-HSD showed a nonlinear increase in DNA damage. Moreover, Fe-HSD presented 0.6-fold more DNA damage compared with SD (p = 0.0055) in the 1st month of treatment. At months 2 and 3, results show a ≥ 1.4-fold increase in HSD and Fe-HSD DNA damage, respectively, compared with SD (p < 0.01). At the end of the experiment, only HSD DNA damage differed from SD (1.5-fold more, p = 0.0196). Fe supplementation did not aggravate the invert sugar-induced DNA damage (p > 0.05). In the pancreas, results showed no differences in DNA damage. Mutagenicity, evaluated by micronucleus testing, was not observed regardless of treatment (p = 0.428). Fe supplementation, in the evaluated concentration, did not aggravate weight gain, impaired glucose tolerance, and sugar overload-induced genotoxicity in rats.

Repair-Assisted Damage Detection Reveals Biological Disparities in Prostate Cancer between African Americans and European Americans.

Simple SummaryProstate cancer is the most diagnosed cancer among men in the United States. African American men are diagnosed with and succumb to prostate cancer at higher rates than other demographic groups. Previously published works described the biological differences in prostate tumors that may contribute to poorer outcomes in African American men compared to European American men. This study was designed to explore the DNA lesion profiles found in prostate tissues. Using tissue microarrays, we found that prostate tumors from African American patients have more uracil and pyrimidine damage, elevated UNG levels, and reduced XRCC1 levels than European American tumors, which may indicate defects in the base excision repair pathway. In addition, these men had higher UMP and lower expression of folate cycle metabolites, suggesting that metabolic rewiring may also contribute to the dysregulation of base excision repair.African Americans (AA) are two times more likely to be diagnosed with and succumb to prostate cancer (PCa) compared to European Americans (EA). There is mounting evidence that biological differences in these tumors contribute to disparities in patient outcomes. Our goal was to examine the differences in DNA damage in AA and EA prostate tissues. Tissue microarrays with matched tumor-benign adjacent pairs from 77 AA and EA PCa patients were analyzed for abasic sites, oxidative lesions, crosslinks, and uracil content using the Repair Assisted Damage Detection (RADD) assay. Our analysis revealed that AA PCa, overall, have more DNA damage than EA PCa. Increased uracil and pyrimidine lesions occurred in AA tumors, while EA tumors had more oxidative lesions. AA PCa have higher levels of UMP and folate cycle metabolites than their EA counterparts. AA PCa showed higher levels of UNG, the uracil-specific glycosylase, than EA, despite uracil lesions being retained within the genome. AA patients also had lower levels of the base excision repair protein XRCC1. These results indicate dysfunction in the base excision repair pathway in AA tumors. Further, these findings reveal how metabolic rewiring in AA PCa drives biological disparities and identifies a targetable axis for cancer therapeutics.

Evidence of chromosomal damage in scleroderma

Evidence of chromosomal damage in scleroderma

Analysis of Differences in DNA Damage and Repair Efficacy in Lymphocytes of Patients with Bipolar Disorder.

The aim of this study was to determine DNA damage during euthymic and attack periods, and the oxidative metabolism states that may cause this damage in the pathophysiology of bipolar disorder. The role of DNA repair mechanisms in this process was also investigated. The study included a total of 90 patients aged between 18-65 years who were diagnosed with bipolar disorder according to DSM- 5 diagnostic criteria, with 30 patients in euthymic, 30 in manic and 30 in depressive periods. A control group was formed of 30 healthy subjects matched to the patients by age, gender, body mass index and smoking status and/or alcohol consumption. Oxidative metabolism was investigated using the Comet Assay technique to assess DNA damage, according to the oxidant/antioxidant status in the technique developed by Erel with the Rel ASSAY Diagnostics kit (Turkey). The control and patient groups were compared in respect of gene expression levels of OGG1 and NEIL1 repair genes at mRNA level with Real-Time PCR. Increased DNA damage was found in the euthymic and manic groups and decreased NEIL1 gene expression in the depressive group. The oxidative stress index was found to be decreased in the patient groups compared to the healthy control group. Oxidative imbalance and DNA damage and repair disorders may be effective in the pathophysiology of bipolar disorder. Further studies on this subject are required to clarify the etiology and new treatment goals.

Analysis of Differences in DNA Damage and Repair Efficacy in Lymphocytes of Patients with Bipolar Disorder

The aim of this study was to determine DNA damage during euthymic and attack periods, and the oxidative metabolism states that may cause this damage in the pathophysiology of bipolar disorder. The role of DNA repair mechanisms in this process was also investigated.The study included a total of 90 patients aged between 18-65 years who were diagnosed with bipolar disorder according to DSM- 5 diagnostic criteria, with 30 patients in euthymic, 30 in manic and 30 in depressive periods. A control group was formed of 30 healthy subjects matched to the patients by age, gender, body mass index and smoking status and/or alcohol consumption. Oxidative metabolism was investigated using the Comet Assay technique to assess DNA damage, according to the oxidant/antioxidant status in the technique developed by Erel with the Rel ASSAY Diagnostics kit (Turkey). The control and patient groups were compared in respect of gene expression levels of OGG1 and NEIL1 repair genes at mRNA level with Real-Time PCR.Increased DNA damage was found in the euthymic and manic groups and decreased NEIL1 gene expression in the depressive group. The oxidative stress index was found to be decreased in the patient groups compared to the healthy control group.Oxidative imbalance and DNA damage and repair disorders may be effective in the pathophysiology of bipolar disorder. Further studies on this subject are required to clarify the etiology and new treatment goals.