Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"title":"Increased genotoxic damage in Sicilian donkeys reared in different conditions of air quality","authors":"Emanuele D'Anza ,&nbsp;Ilaria Cascone ,&nbsp;Flavio Luongo ,&nbsp;Sara Albarella ,&nbsp;Francesca Ciotola ,&nbsp;Luigi Liotta ,&nbsp;Vincenzo Peretti","doi":"10.1016/j.mrgentox.2025.503899","DOIUrl":"10.1016/j.mrgentox.2025.503899","url":null,"abstract":"<div><div>This study investigates chromosomal damage in donkeys to assess the impact of long-term exposure to different concentrations of environmental genotoxic agents, which pose health risks to animals and humans by promoting DNA breaks. The genotoxic damage was assessed through aneuploidy, chromosomal aberrations (CAs), and sister chromatid exchanges (SCEs) tests in donkeys, crossbred Ragusano and Grigio Siciliano breeds, from three areas in the Sicily region (Italy) with different levels of air pollution. Donkeys from areas with higher concentrations of fine particulate matter and nitrogen dioxide showed significantly elevated levels of aneuploidy and chromosomal abnormalities compared to those from less polluted areas. These findings provide the first evidence in donkeys of the combined effects of long-term exposure to airborne pollutants on genomic stability. This study reinforces the potential use of donkeys as effective biomonitoring organisms for evaluating environmental health risks and genotoxic damage under different pollution conditions.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503899"},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chernobyl as a natural laboratory: Genetic instability, adaptation, and ecological recovery in flora and fauna under chronic radiation","authors":"Gulsah Yildiz Deniz","doi":"10.1016/j.mrgentox.2025.503898","DOIUrl":"10.1016/j.mrgentox.2025.503898","url":null,"abstract":"<div><div>The Chernobyl nuclear accident of April 1986 remains the most severe nuclear disaster in human history, with long-lasting consequences for ecosystems exposed to chronic ionizing radiation. In the decades since the event, the Chernobyl Exclusion Zone has become an unintended but invaluable natural laboratory for investigating the genetic and ecological effects of persistent radiation exposure. This review synthesizes current knowledge on both immediate and long-term biological consequences observed in plants and animals inhabiting contaminated areas. Initial impacts included acute mortality, reproductive failure, and ecosystem collapse, most notably exemplified by the “Red Forest.” Over subsequent years, studies revealed elevated mutation rates, chromosomal aberrations, genomic instability, and heritable genetic damage across diverse taxa. At the same time, evidence of adaptive responses has emerged, including increased antioxidant defenses, epigenetic modifications, and phenotypic changes such as melanism in amphibians. Flora and fauna within the exclusion zone illustrate the dual narrative of vulnerability to mutagenic stress and resilience through evolutionary adaptation. Comparisons with the Fukushima accident demonstrate convergent biological responses across ecosystems while highlighting the importance of context, such as terrestrial versus marine contamination and remediation strategies. Future research must integrate advanced genomic and epigenomic tools, accurate dosimetry, and long-term monitoring to clarify thresholds for harmful versus adaptive outcomes. Chernobyl thus continues to provide critical insights into radiation biology, ecological recovery, and evolutionary toxicology under conditions of chronic environmental stress.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503898"},"PeriodicalIF":2.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of γ-H2AX foci, micronucleus formation, and radiation dose to the blood lymphocytes in pediatric and adult participants underwent computed tomography imaging","authors":"Divya K. Mohan ,&nbsp;Nandhini K. ,&nbsp;Aishwarya S. ,&nbsp;Senthil Kumar M. ,&nbsp;Swetha K. ,&nbsp;Akshaya J. ,&nbsp;Sudha Pattan ,&nbsp;Venkata Sai P.M. ,&nbsp;Venkateswarlu Raavi ,&nbsp;Venkatachalam Perumal","doi":"10.1016/j.mrgentox.2025.503897","DOIUrl":"10.1016/j.mrgentox.2025.503897","url":null,"abstract":"<div><div>Computed tomography (CT) is a widely used diagnostic imaging modality that contributes significantly to human healthcare. Despite the advantage, its extensive use increased concerns due to receiving radiation doses to pediatric patient's over adults during CT imaging. We evaluated the biological effects (Gamma-H2AX (γ-H2AX) foci and micronucleus (MN) formation) of low-dose X-radiation on the peripheral blood lymphocytes of pediatric (n = 45) and adult (n = 38) participants before and after CT imaging. Participant-specific organ doses were calculated using VirtualDose™CT software, weighted to the corresponding organ's blood volume, summed to derive the blood dose, and then related to induced DNA damage. A significant (p &lt; 0.001) increase in γ-H2AX foci and MN frequencies was observed in both pediatric and adult groups after CT imaging. While the mean effective dose (ED) in pediatric and adult (16.21 ± 11.33 mSv and 31.30 ± 16.25 mSv) participants were significantly different (p &lt; 0.001), the mean blood doses did not differ (9.83 ± 6.34 mGy and 12.82 ± 5.96 mGy) (p &gt; 0.05), respectively. A weak correlation was observed between the induced DNA damage to that of ED and blood dose. The results suggest that damage to blood lymphocytes after CT imaging was observed by an increased γ-H2AX foci result of DNA double-strand breaks. The increase in MN frequency suggests activation of DNA repair, thereby contributing to minimal damage, although they are unstable. Therefore, it is necessary to follow up on the pediatric participants to look for stable aberrations to better relate DNA damage to exposure and long-term health effects, if any.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503897"},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA damage and nuclear anomalies in peripheral blood lymphocytes from asthma patients and obese individuals","authors":"Aswathi Pootheri ,&nbsp;Medha Nagaraj ,&nbsp;Nethra Raghuraman ,&nbsp;Sohini Dey ,&nbsp;Swathi R ,&nbsp;Sombodhi Bhattacharya ,&nbsp;Yeshi Yangchen ,&nbsp;S. Santoshi Iyer ,&nbsp;Mohnish Ram G ,&nbsp;Narmada Ashok ,&nbsp;Wilner Martinez Lopez ,&nbsp;Radha Saraswathy","doi":"10.1016/j.mrgentox.2025.503889","DOIUrl":"10.1016/j.mrgentox.2025.503889","url":null,"abstract":"<div><div>Asthma is a chronic, non-communicable respiratory disorder affecting approximately 262 million people worldwide, with India projected to become one of the leading countries in prevalence. Asthma is well-established as a condition of chronic inflammation of the airways and related to systemic oxidative stress, but relatively not much is known about the genomic instability associated with asthma. On the other hand, obesity is found in 650 million people worldwide and 113 million people in India. Studies reported links between asthma and obesity, which include adipose tissue dysfunction and inefficient blood monocyte efferocytosis. Obesity enhances reactive oxygen species (ROS) production and inflammation, leading to DNA lesions. Thus, the aim of this study was to assess the DNA damage and frequencies of micronuclei (MNi), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in the lymphocytes of asthma patients and obese individuals. This study evaluates the DNA damage and nuclear anomalies in (n = 435) subjects (asthma patients n = 100, asthmatic obese patients n = 131, obese n = 100 and controls n = 104). An alkaline comet assay was used to assess DNA damage and nuclear anomalies were assessed by cytokinesis block micronucleus cytome (CBMN-Cyt) assay. All subjects were recruited between the age of 20 and 60 years. The total DNA damage, MNi, and frequency of total nuclear anomalies were found to be significantly higher in asthma male and female patients, asthmatic obese male and female patients, and obese males and females in comparison to control males and females (p &lt; 0.05). The total comet score showed a positive correlation with the frequency of total nuclear anomalies in asthma male and female patients and obese males, respectively. Overall the findings demonstrate that inflammation and oxidative stress in asthma and obesity lead to DNA damage and genomic instability.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503889"},"PeriodicalIF":2.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular uptake, induction of reactive oxygen species, and genotoxicity of differently sized cobalt oxide nanoparticles in human peripheral blood mononuclear cells in vitro","authors":"Milda Babonaitė,&nbsp;Veronika Dedonytė,&nbsp;Emilija Striogaitė,&nbsp;Juozas R. Lazutka","doi":"10.1016/j.mrgentox.2025.503888","DOIUrl":"10.1016/j.mrgentox.2025.503888","url":null,"abstract":"<div><div>Cobalt (II, III) oxide nanoparticles (Co₃O₄-NPs) have potential applications in different technological and medical fields, including drug delivery and as novel anticancer treatments. However, widespread application could lead to a high-level direct human exposure, raising concerns about their genotoxic potential. This study aimed to evaluate the cytotoxicity and genotoxicity of Co₃O₄-NPs in human peripheral blood mononuclear cells (PBMCs) <em>in vitro.</em> Two sizes of Co₃O₄-NPs (10–30 nm and &lt; 50 nm) were tested to understand any size-dependent differences in genotoxicity. The study measured NP uptake, reactive oxygen species (ROS) generation, cell viability, DNA strand breaks, micronuclei formation, and sister chromatid exchange to assess the cyto-genotoxic potential of Co₃O₄-NPs. Flow cytometric analysis revealed that Co₃O₄-NPs with a primary size of &lt; 50 nm were more efficiently internalized by human PBMCs and induced higher ROS levels than 10–30 nm particles. Both nanoparticles’ sizes induced significant primary DNA damage at non-cytotoxic concentrations, often in a dose-dependent manner. Cytogenetic analysis demonstrated that Co₃O₄-NPs exert genotoxic effects, with &lt; 50 nm NPs inducing more significant DNA damage and reduced cell viability than smaller nanoparticles. Additionally, interindividual differences in response to exposure to Co₃O₄–NPs were observed. The study findings suggest that Co₃O₄-NPs possess genotoxic potential in human PBMCs <em>in vitro</em>, raising safety concerns about their use. This highlights the need for comprehensive genotoxicity assessments of Co₃O₄-NPs in different cell types.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503888"},"PeriodicalIF":2.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective role of Cockayne Syndrome B (CSB) protein in maintaining genome integrity in human cells under oxidative stress","authors":"Grace Kah Mun Low,&nbsp;Gavin Yong-Quan Ng,&nbsp;Dimphy Zeegers,&nbsp;Aloysius Ting,&nbsp;Kalpana Gopalakrishnan,&nbsp;Aik Kia Khaw,&nbsp;Manikandan Jayapal,&nbsp;Manoor Prakash Hande","doi":"10.1016/j.mrgentox.2025.503887","DOIUrl":"10.1016/j.mrgentox.2025.503887","url":null,"abstract":"<div><div>Cockayne Syndrome (CS), a progeroid disorder characterised by premature ageing and neurodevelopmental abnormalities, is primarily caused by mutations in the CSB protein, a key component of the transcription-coupled nucleotide excision repair pathway. This study investigates the role of CSB in managing oxidative DNA damage and preserving telomere integrity under oxidative stress. Using CSB-deficient human fibroblasts (CS-B) and matched controls, we exposed cells to acute and chronic oxidative stress via hydrogen peroxide (H₂O₂) and elevated oxygen (40 %) levels. CS-B fibroblasts showed relative resistance to acute oxidative stress in terms of cell death, maintaining viability and displaying limited cell cycle arrest. In contrast, chronic oxidative exposure induced accelerated senescence in CS-B cells, evidenced by increased telomere attrition, senescent morphology, and early activation of senescence-associated β-galactosidase associated with increased DNA damage and aberrant DNA repair. Gene expression profiling revealed downregulation of key DNA repair and cell cycle genes in CS-B fibroblasts following H₂O₂ treatment, indicating impaired damage response pathways. These findings highlight the essential role of CSB in genome maintenance and suggest that its loss contributes to CS pathology through heightened sensitivity to chronic oxidative stress and telomere dysfunction. This work enhances our understanding of CS-related cellular mechanisms and may inform future therapeutic strategies targeting oxidative stress and DNA repair.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503887"},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotoxicity mode of action exploration of polyethylene glycol terephthalate (PET) acetic acid migration solution under repeated-dose exposure in rats","authors":"Liang Wang ,&nbsp;Li Cao ,&nbsp;Xiaoya Wang ,&nbsp;Yufei Liu ,&nbsp;Weiwei Zhang ,&nbsp;Yurui Gou ,&nbsp;Jun He ,&nbsp;Jiao Huo ,&nbsp;Xiaomeng Li ,&nbsp;Jinyao Chen","doi":"10.1016/j.mrgentox.2025.503886","DOIUrl":"10.1016/j.mrgentox.2025.503886","url":null,"abstract":"<div><div>As a commonly used material that contacts food, polyethylene glycol terephthalate (PET) may interact with food, and since certain components can migrate, this has become a food safety concern. This study aims to investigate the genotoxicity of PET acetic acid migration solution and its toxic mode of action using an <em>in vivo</em> multi-endpoint genotoxicity evaluation system and quantitative liver proteomics analysis. Forty-eight male Sprague–Dawley rats were randomly divided into eight groups: the PET acetic acid migration solution group, the acetic acid group, the phosphate-buffered saline (PBS) control group, the N-ethyl-N-nitrosourea (ENU) positive control group, and their corresponding satellite groups. PBS and ENU were administered by gavage, while the PET acetic acid migration solution and acetic acid were administered orally in the drinking water. The exposure duration was 35 days, followed by a recovery period of 15 days. The PET acetic acid migration solution can cause heart, liver, and kidney injury in rats. On the 15th day, mutations were seen in the <em>Pig-a</em> gene test. On the 35th day, DNA damage was observed in peripheral blood and liver cells. Gene ontology (GO) analysis of the liver proteomics revealed enrichment in DNA metabolism and binding processes, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the DNA replication pathway. Immunohistochemical analysis demonstrated a significant increase in 8-hydroxydeoxyguanosine (8-OHdG) and a decrease in single-stranded-binding (SSB) protein in the PET acetic acid migration solution group. In summary, the PET acetic acid migration solution has the potential to induce DNA damage, possibly by inhibiting DNA replication and DNA repair pathways. However, the likelihood of genetic toxicity is low.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503886"},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of nicotinamide mononucleotide on DNA damage and cell death in A549 cells and aging in C. elegans caused by hydrogen peroxide","authors":"Chuncao He ,&nbsp;Xueying Sun ,&nbsp;Ting Xu ,&nbsp;Xiaoqiang Hu ,&nbsp;Jinyi Han ,&nbsp;Kexin Xu ,&nbsp;Qin Song ,&nbsp;Ting Duan ,&nbsp;Jun Yang","doi":"10.1016/j.mrgentox.2025.503885","DOIUrl":"10.1016/j.mrgentox.2025.503885","url":null,"abstract":"<div><div>Oxidative stress is a major factor for aging. Nicotinamide mononucleotide (NMN) is a naturally occurring bioactive nucleotide and a precursor for nicotinamide adenine dinucleotide (NAD⁺), and accumulating evidences have shown that NMN is a promising anti-aging agent, however, the underlying molecular mechanisms remain to be elucidated. Therefore, in the current study, the protective effects of NMN on oxidative stress-induced damage to cells, in particular, the various types of cell death induced by oxidative stress, were evaluated. It was found that NMN inhibited hydrogen peroxide (H₂O₂)-induced decrease in A549 cell viability·H₂O₂-triggered reactive oxygen species (ROS) production was also diminished by NMN. Furthermore, results from 8-hydoxy 2 deoxyguanosine (8-OHdG) level, alkaline comet assay, and γ-H2AX foci formation indicated that NMN protected cells from H₂O₂-induced DNA damage. Detailed cell death analysis revealed that H₂O₂ caused A549 cell death mainly through apoptosis and ferroptosis, but not necroptosis or parthanatos, and NMN could effectively inhibit the apoptosis and ferroptosis pathways, thus protected cells from H₂O₂-induced cell death. Finally, we validated NMN protected against H₂O₂-induced organismal senescence in <em>C. elegans</em>. Taken together, these results suggests that NMN is a potent agent against oxidative stress, which could contribute to its anti-aging effects.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503885"},"PeriodicalIF":2.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perchloroethylene: Genotoxicity and cytotoxicity in human peripheral blood lymphocytes in vitro","authors":"Tülay Aşkın Çelik ,&nbsp;Ümit Ünsal","doi":"10.1016/j.mrgentox.2025.503884","DOIUrl":"10.1016/j.mrgentox.2025.503884","url":null,"abstract":"<div><div>Perchloroethylene (PCE), a widely used solvent, is classified as a probable human carcinogen. We have studied its genotoxicity, clastogenicity, and cytotoxicity in cultured human peripheral lymphocytes (HPLs). Cytogenetic tests used were the chromosomal aberration (CA), sister chromatid exchange (SCE), mitotic index (MI), replication index (RI), and micronucleus (MN) assays. Positive results were obtained with each of these assays: a dose-dependent increase in CA, a significant increase in SCE, a significant decrease in MI and RI, and an increase in MN frequency at the highest concentration of PCE. These results demonstrate that PCE induces significant genotoxic and clastogenic effects in human peripheral lymphocytes.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503884"},"PeriodicalIF":2.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PPAR-β/δ agonist GW0742 alleviates DNA damage and lupus nephritis in an animal model of systemic lupus erythematosus via restoring DNA repair gene expression","authors":"Mohamed S.M. Attia ,&nbsp;Mohammed A. Al-Hamamah ,&nbsp;Sheikh F. Ahmad ,&nbsp;Ahmed Nadeem ,&nbsp;Saleh A. Bakheet ,&nbsp;Mushtaq A. Ansari ,&nbsp;Gamaleldin I. Harisa ,&nbsp;Talha Bin Emran ,&nbsp;Sabry M. Attia","doi":"10.1016/j.mrgentox.2025.503881","DOIUrl":"10.1016/j.mrgentox.2025.503881","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a persistent autoimmune inflammatory disease associated with an elevated risk of kidney damage. The etiology of SLE remains unclear; nevertheless, current investigations increasingly indicate that increased DNA damage and deficiencies in the mechanisms of its repair might contribute to its pathogenesis, necessitating the identification and management of the disease. Therapies for SLE have improved considerably over recent decades. However, drugs that specifically address the underlying pathogenic pathways, such as potential DNA repair deficiencies, are unavailable. In this situation, drugs that ameliorate the altered DNA damage/repair might be a possible option for treating SLE. We investigated whether GW0742, an agonist of the peroxisome proliferator activator receptor β/δ, improves kidney function and ameliorates DNA damage/repair alteration in female lupus-prone mice. The results demonstrate that the repeated administration of GW0742 significantly ameliorates DNA damage/repair alteration in the bone marrow cells of lupus-prone animals, as assessed by the comet test. Furthermore, the administration of GW0742 restored the impaired DNA damage/repair pathway in lupus-prone mice by decreasing Gadd45a and p53 expression while elevating Ogg1 and Parp1 in the kidney tissues. The administration of GW0742 recovered the disturbed kidney redox balance in lupus-prone mice. It also ameliorated the altered biochemical markers related to lupus nephritis, as demonstrated by reduced levels of urinary protein and albumin, serum creatinine, and BUN. GW0742's protective outcome was verified by its ability to diminish the increased inflammatory marker MPO activity and ameliorated kidney histological characteristics of SLE. This suggests that GW0742 is a promising novel therapeutic agent for managing SLE and its associated complications.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503881"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}