Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"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}

{"title":"Epistatic interactions in DNA repair genes as biomarkers of susceptibility for DNA damage in pesticide-exposed agricultural workers of Punjab, North-West India","authors":"Karashdeep Kaur ,&nbsp;Rupinder Kaur","doi":"10.1016/j.mrgentox.2025.503880","DOIUrl":"10.1016/j.mrgentox.2025.503880","url":null,"abstract":"<div><div>Some occupational exposures to pesticides have been associated with genotoxicity which arises from DNA single-strand breaks (SSBs), repair of DNA double-strand breaks (DSBs), DNA adduct formation, or DNA-DNA and DNA-protein cross-links. Polymorphisms in genes encoding enzymes of DNA repair pathways may modulate the individual’s susceptibility to pesticide-induced genotoxicity. A total of 450 subjects were included in this study, which comprises 225 agricultural workers exposed to complex mixtures of pesticides and 225 non-exposed controls from Punjab, North-West India. Susceptibility of <em>OGG1</em> Ser326Cys (C1245G), <em>XRCC1</em> Arg194Trp (C26304T), <em>XRCC1</em> Arg399Gln (G28152A), <em>XPC</em> Lys939Gln (A2920C), <em>XPC</em> Ala499Val (C21151T), <em>XPD</em> Asp312Asn (G23591A), <em>XPD</em> Lys715Gln (A35931C), <em>XPF</em> Arg415Gln (G1244A), <em>XPG</em> Asp1104His (G3507C), <em>ERCC1</em> 3′-UTR (C8092A) and <em>ERCC1</em> Asn118Asn (C354T) gene polymorphisms with pesticide-induced DNA damage was determined by Kruskal-Wallis test. The association of epistatic gene interactions with DNA damage was studied by ANOVA. The results indicated significant interactions of variant <em>OGG1</em> 326Ser/Cys genotype with <em>XRCC1</em> 194Arg/Trp and <em>XRCC1</em> 399Arg/Gln genotypes in increased susceptibility to DNA damage. <em>XPC</em> 939Gln/Gln genotype significantly interacts with <em>XPC</em> 499Ala/Val, <em>XPD</em> 312Asp/Asp and <em>XPD</em> 715Gln/Gln variant genotypes to increase DNA damage susceptibility. Among exposed <em>XPF</em> 415Gln/Gln individuals, DNA damage was significantly higher in those individuals who had variant <em>XPG</em> Asp/His and <em>ERCC1</em> 8092CA genotypes. We observed some statistically significant epistatic gene interactions in DNA repair pathways in modulating DNA damage, which may be used as biomarkers of susceptibility in pesticide-exposed agricultural workers of Punjab, North-West India.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503880"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773162","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":"Comparison of different techniques for γH2AX/pH3 biomarkers quantification for chemical genotoxicity assessment","authors":"Cynthia Recoules ,&nbsp;Chloé Huertas ,&nbsp;Julien Vignard,&nbsp;Marc Audebert","doi":"10.1016/j.mrgentox.2025.503878","DOIUrl":"10.1016/j.mrgentox.2025.503878","url":null,"abstract":"<div><div>Chemical risk assessment relies on <em>in vitro</em> genotoxicity tests. Histone modifications (γH2AX and pH3) have emerged as valuable biomarkers for genotoxicity detection. In this study, we compared three parameters (global intensity, nuclear intensity, and foci number) for the γH2AX biomarker and two parameters (global intensity and % cell in mitosis) for the pH3 biomarker. These analyzes were performed in three cell lines: human osteosarcoma U2OS cells, human hepatocellular carcinoma HepG2 cells and rat intestinal epithelial IEC-6 cells. Cells were exposed for 24 h to four well-characterized hazardous substances: nocodazole (aneugen), etoposide (topoisomerase inhibitor), benzo[<em>a</em>]pyrene (DNA adducts inducer), and tunicamycin (apoptosis inducer). The Benchmark Concentration (BMC) approach indicated that the sensitivity of the technics varied depending on both the chemical compounds and the tested cell line. The γH2AX foci analysis provided the higher sensitivity for clastogenic compounds. For the aneugenic compound, the global intensity and the proportion of mitotic cells showed similar sensitivity. Following tunicamycin treatment, we only detected increase in γH2AX nuclear intensity in U2OS cell model, indicating that apoptosis does not interfere with γH2AX global intensity or foci number, thereby minimizing the risk of false positive results. Finally, we observed that compared to the other methods, global intensity permitted to monitor weaker fold inductions of the biomarkers. By comparing the different quantification methods of histone modifications used as genotoxicity biomarkers, this study highlights the most suitable parameters to be used.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503878"},"PeriodicalIF":2.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704717","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":"Investigation of chemicals with inconsistent Ames results using miniaturized Ames test systems","authors":"Csaba Boglári,&nbsp;Cécile Koelbert,&nbsp;Nicole Weiland-Jaeggi","doi":"10.1016/j.mrgentox.2025.503874","DOIUrl":"10.1016/j.mrgentox.2025.503874","url":null,"abstract":"<div><div>The Ames assay is a bacterial reverse gene mutation test that has been a cornerstone of mutagenicity assessment. The emphasis now is on developing miniaturized versions of the Ames test in Petri dish to require less chemicals, reagents, and liver microsomal S9 fraction, thus reducing the number of test animals needed and to better comply with 3R principles. Miniaturized Ames assay versions promote high throughput testing of multiple samples during compound screening and facilitate the early exclusion of genotoxic agents during the product development process. Existing experimental data shed light on a high concordance between results gained with miniaturized Ames tests and the Petri dish-based method, yet further testing is required to corroborate these findings. We selected compounds with previously reported inconsistent outcomes and assessed their mutagenic potential using two miniaturized Ames assay formats, an agar-based 6-well plate test, and a liquid microplate fluctuation format assay. Investigation of dose-response curves of known mutagens with varying bacterial cell density inputs revealed that the sensitivity of the 6-well agar plate format might be increased by applying the right bacterial cell density. Our analysis indicates an overall good correlation between the results acquired with the two miniaturized Ames assay formats despite the conceptual characteristic differences in the assay paradigms. Furthermore, the miniaturized Ames assay formats could detect several chemicals as positive at lower concentrations than the Petri dish-based assay. Our findings indicate that the miniaturized Ames assay variations show promise as a reliable method for assessing chemical mutagenicity, while also aligning with environmentally friendly testing strategies. Finally, our results show that the miniaturized assays may exhibit increased sensitivity to impurities, potentially contributing to the observed discrepancies in the obtained results.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503874"},"PeriodicalIF":2.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663223","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":"Photogenotoxicity of N-nitrosoproline plus simultaneous UVA irradiation in human-derived keratinocytes","authors":"Naomi Tomozane ,&nbsp;Noriko Tanaka ,&nbsp;Sakae Arimoto-Kobayashi","doi":"10.1016/j.mrgentox.2025.503876","DOIUrl":"10.1016/j.mrgentox.2025.503876","url":null,"abstract":"<div><div>In this study, we investigated the genotoxicity of <em>N</em>-nitrosoproline (NPRO) in human-derived keratinocytes (HaCaT and NCTC2544 cells) using simultaneous UVA irradiation without metabolic activation. NPRO plus UVA exhibited dose- and intensity-dependent micronuclei formation in the keratinocytes, as well as nitric oxide (NO) production. The action spectra of genotoxicity and NO formation from NPRO plus UVA followed the absorption curve of NPRO, indicating that photoenergy was absorbed by the NPRO-triggered photoreaction. A significant increase in cyclic guanosine monophosphate (cGMP) was observed in HaCaT cells treated with NPRO plus UVA. NO production from UVA-irradiated NPRO paralleled micronuclei formation, and the phototoxicity of NPRO may have simultaneously interfered with the cGMP-related signaling systems caused by NO from photoactivated NPRO.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503876"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631903","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":"Significant new developments in genetic toxicology testing","authors":"Miroslav Mišík,&nbsp;P. David Josephy,&nbsp;Helga Stopper,&nbsp;Siegfried Knasmueller","doi":"10.1016/j.mrgentox.2025.503873","DOIUrl":"10.1016/j.mrgentox.2025.503873","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503873"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680603","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":"Bleomycin induces short-term telomere fragility in Epstein-Barr virus-transformed human lymphoblastoid cells","authors":"Andrea G. Cardozo ,&nbsp;Daniel C. Castrogiovanni ,&nbsp;Julieta M. Parisi ,&nbsp;Alejandro D. Bolzán","doi":"10.1016/j.mrgentox.2025.503877","DOIUrl":"10.1016/j.mrgentox.2025.503877","url":null,"abstract":"<div><div>The induction of telomere dysfunction-related chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) was studied in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). To this end, an EBV-induced lymphoblastoid cell line (T-37) was exposed to increased concentrations of BLM (10–100 µg/mL) for 2 h at 37ºC, and telomere aberrations were analyzed 24 h (first mitosis) after treatment using PNA-FISH with pan-telomeric plus pan-centromeric probes. Telomere signal duplications (TSD) increased significantly in BLM-exposed cells (p &lt; 0.01), although the concentration-response relationship was non-linear. Most of the induced TSD (95–99 %) were of chromatid-type. No induction of telomere signal loss, telomere fusions or telomere associations by BLM was observed in T-37 cells. These findings show that BLM induces short-term telomere dysfunction in EBV-transformed human lymphoblastoid cells in the form of TSD (which implies telomere fragility) and suggest that these effects mainly occur during the G2 stage of the cell cycle. The persistence of this type of aberrations in the long-term in EBV-induced lymphoblastoid cells and other human cells exposed to BLM may be of medical relevance. Telomere fragility induced by BLM could promote genomic instability, which might contribute to the development of secondary tumors in patients undergoing chemotherapy based on this compound. Consequently, our study raises concerns about the potential long-term genomic effects of BLM in treated patients and suggests that the analysis of TSD could be a useful biomarker for detecting BLM-induced telomere dysfunction in human cells.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503877"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654210","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":"Genome-wide mutation analysis induced by mutagens in TK6 cells using Hawk-Seq™","authors":"Yuki Otsubo ,&nbsp;Takako Hirose ,&nbsp;Shoji Matsumura ,&nbsp;Sayaka Hosoi ,&nbsp;Kazutoshi Saito ,&nbsp;Masaaki Miyazawa","doi":"10.1016/j.mrgentox.2025.503875","DOIUrl":"10.1016/j.mrgentox.2025.503875","url":null,"abstract":"<div><div>Error-corrected next-generation sequencing (ecNGS) sensitively detects rare mutations in biological models. We applied Hawk-Seq™ to evaluate chemical-induced mutations using the IVGT TK6 human lymphoblastoid cell line. Since clonal and sub-clonal variants (CVs and SCVs) decrease mutation detection sensitivity, we first identified 4,501,430 CVs compared to GRCh38 by resequencing the TK6 genome. The overall base substitution (BS) frequency in vehicle controls after filtering out these variants was 2.0 × 10⁻⁶ base pairs (bp), relatively higher than in other ecNGS studies. A total of 4974 sites provided the same types of BSs in ≥ 2 vehicle controls, suggesting that SCVs increased the error frequency. After filtering out these sites, the overall background BS frequency significantly decreased (0.93 × 10⁻⁶ bp). Therefore, we filtered out the potential SCV positions identified using resequencing data with increased depth (mean depth of ca. 110), reducing the background overall BS frequency to 0.65 × 10⁻⁶ bp. Finally, we evaluated DNA samples from TK6 cells exposed to <em>N</em>-methyl-<em>N</em>-nitrosourea (MNU) and <em>N</em>-ethyl-<em>N</em>-nitrosourea (ENU) for 24 h. The overall BS frequencies in MNU- and ENU-treated samples were 9.0 × 10⁻⁶ and 2.0 × 10⁻⁶ bp, respectively, significantly improving the signal-to-noise ratio. MNU predominantly induced G:C &gt; A:T (21 × 10⁻⁶ bp), 62 times higher than that induced by vehicle controls. ENU primarily induced G:C &gt; A:T (2.7 × 10⁻⁶ bp) and significantly increased A:T &gt; C:G and A:T &gt; G:C frequencies (∼10⁻⁷ bp). Our method sensitively detected mutations, including minor patterns, indicating its potential to reflect various mutagenic mechanisms.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503875"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654211","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":"Radiology personnel chronically exposed to low-dose ionizing radiation: Assessment of genotoxic damage with the buccal micronucleus cytome assay","authors":"Serap Yüce Emiroğlu ,&nbsp;Tülay Aşkın Çeli̇k","doi":"10.1016/j.mrgentox.2025.503872","DOIUrl":"10.1016/j.mrgentox.2025.503872","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to assess the genotoxic effects of chronic occupational exposure to low-dose ionizing radiation among healthcare professionals employed at three hospitals in Aydın, Turkey: Aydın Adnan Menderes University Research and Application Hospital (ADU-UAH), Atatürk State Hospital, and Aydın State Hospital. The exposed group comprised 27 healthcare workers routinely operating in radiation-related departments, while 27 matched individuals with no known exposure constituted the control group.</div></div><div><h3>Methods</h3><div>Genetic damage was evaluated using the exfoliated buccal micronucleus cytome (BMCyt) assay, a validated and non-invasive method for human biomonitoring. Frequencies of nuclear abnormalities—including micronuclei, binucleated cells, nuclear buds, condensed chromatin, karyorrhexis, karyolysis, and pyknotic cells—were systematically recorded and compared between groups.</div></div><div><h3>Results</h3><div>A statistically significant increase in all genotoxic markers was observed in the exposed group compared to controls (p &lt; 0.05). The highest frequency of micronucleated cells was found in workers at Aydın State Hospital (32.38 ‰), approximately 30-fold higher than the control group (2.84 ‰). Healthcare workers at ADU-UAH and Atatürk State Hospital exhibited moderate yet notable elevations, with frequencies of 24.85 ‰ and 17.28 ‰, respectively. Sex-stratified analysis revealed minor but statistically significant differences, with male workers showing slightly higher genotoxicity levels (p &lt; 0.05), although female staff exhibited higher nuclear anomalies at certain institutions.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that chronic exposure to low-dose ionizing radiation is associated with increased genomic instability among healthcare workers. The elevated frequency of nuclear abnormalities highlights a potential long-term mutagenic risk in occupational settings. These results underscore the urgent need for reinforced radiation safety protocols, routine biomonitoring, and institutional policy revisions to mitigate genotoxic risks. Further studies are warranted to elucidate the mechanisms underlying radiation-induced genomic damage and to better understand individual susceptibility patterns in exposed populations.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503872"},"PeriodicalIF":2.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290487","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":"Low-dose bisphenol A plus arsenite: Continuous or intermittent exposures in Sprague-Dawley rats; Effects on kidney oxidative stress, DNA damage, ferroptosis, and fibrosis","authors":"Girija Prasanna Sahoo,&nbsp;Asutosh Pattnaik,&nbsp;Vinod Kumar,&nbsp;Gopabandhu Jena","doi":"10.1016/j.mrgentox.2025.503871","DOIUrl":"10.1016/j.mrgentox.2025.503871","url":null,"abstract":"<div><div>Arsenic and bisphenol A (BPA) are widespread environmental pollutants. We have studied the nephrotoxicity of arsenite (ARS), 10 mg/L in drinking water, plus BPA, 50 µg/kg oral dose, in juvenile Sprague-Dawley rats. Animals were randomized into seven groups and exposed to the chemicals either continuously or intermittently, for 8 weeks. The parameters evaluated were urine biomarkers, histopathological and transmission electron microscopic (TEM) examinations, DNA damage (halo assay), and protein expressions. Continuous exposure to AS and BPA significantly increased urinary creatinine, albumin, and total protein, and decreased blood urea nitrogen (BUN). Histopathological and TEM data showed brush border detachment, iron accumulation, podocyte injury, increased slit diaphragm space, and collagen deposition in both exposure groups. Significantly greater DNA damage was seen in the combined-exposure group than in the other experimental groups. Combination exposure in the continuous and intermittent groups showed renal fibrosis and ferroptosis and gene expression analysis revealed a significant increase in Bax and decrease in SIRT 1. Combination exposure was more harmful than the individual exposures in causing kidney injury in these animals.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503871"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887582","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}