Environmental and Molecular Mutagenesis最新文献

{"title":"Urinary Biomarkers of Exposure and Effect in California Schoolchildren From a High Air Pollution Area","authors":"Weihong Guo,&nbsp;Rosemary Castorina,&nbsp;Susan Hurley,&nbsp;Aalekhya Reddam,&nbsp;Robert B. Gunier,&nbsp;Peyton Jacob,&nbsp;Josephine DeGuzman,&nbsp;Jianwen She,&nbsp;Asa Bradman,&nbsp;Nina Holland","doi":"10.1002/em.70061","DOIUrl":"https://doi.org/10.1002/em.70061","url":null,"abstract":"<p>Exposure to air pollution is associated with adverse health effects such as asthma, lung cancer, and cardiovascular diseases. Children are especially vulnerable due to their developing organs, immature immune systems, and higher ventilation rates relative to their body size. Although the adverse health effects of air pollution are well established, the contribution of specific pollutant constituents and the biological mechanisms underlying these effects are not fully understood. This pilot study investigates biomarkers of oxidative stress and inflammation and their association with urinary biomarkers of air pollutant exposure in children. Eighteen children were recruited from an elementary school in Stockton, CA and provided a total of 67 urine samples. Biomarkers of oxidative stress and inflammation were measured using enzyme-linked immunosorbent assays. Liquid chromatography with tandem mass spectrometry was used to measure urinary metabolites of six VOCs and four PAHs. Biomarkers of oxidative stress and inflammation were positively correlated with urinary metabolites of acrylonitrile, acrolein, crotonaldehyde, naphthalene, and fluorene. Two-fold increases in crotonaldehyde and naphthalene metabolite levels were significantly associated with 8-Isop, 8-OHdG and PGE2, with percent-changes ranging from 13%–21% and 11%–16%, respectively. A two-fold increase in crotonaldehyde metabolite level was also significantly associated with a 41% change in CC16. These results suggest that urinary biomarkers of oxidative stress and inflammation may serve as useful tools for assessing chemical exposures and early biological effects in children.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148127865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Analysis of Differentially Expressed Genes in Arsenic-Induced Carcinogenesis and Their Effect on Human Repair Mechanisms","authors":"Lucky Parida,&nbsp;Trupti N. Patel","doi":"10.1002/em.70060","DOIUrl":"https://doi.org/10.1002/em.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Arsenic poisoning significantly elevates the risk of cancer and other chronic illnesses. The goal of this research is to identify important genes whose expression changes in response to arsenic toxicity, and the molecular pathways affected by arsenic, using computational analysis of arsenic toxicity profiles. This approach will computationally identify and analyze genes whose expression changes in response to arsenic, thereby elucidating the heightened risk of carcinogenesis in arsenic-exposed individuals. This work employed high-throughput arsenic toxicity profiles to computationally identify and analyze expressed genes (DEGs) differentially in Affymetrix microarray datasets from the Gene Expression Omnibus (GEO) database, which were screened using the GEO2R program. A protein–protein interaction (PPI) network was constructed using STRING to elucidate the functional links between these DEGs and DNA repair genes. Interactions between the seven central genes (E2F1, EXO1, EZH2, FEN1, HIST1H3A, POLA1, and TIMELESS) and the repair genes PARP1, NBN, PMS1, MSH3, XRCC5, XRCC6, MGMT, and MLH1 were discovered. We employed the DAVID and Enrichr-KG platforms to investigate the functions of these genes and their associations with cellular and molecular processes in greater detail. Two hundred eighty-one non-synonymous single-nucleotide polymorphisms (nsSNPs) in the 07 genes linked to arsenic toxicity were found using the COSMIC database. Based on our analysis, mutations in E2F1, EXO1, EZH2, FEN1, HIST1H3A, POLA1, and TIMELESS can hinder DNA repair mechanisms, ultimately leading to cancer. Our computational analysis demonstrated that these non-synonymous SNPs can affect gene function, potentially altering protein stability and activity. Furthermore, according to Metal-Protein docking and protein–protein docking, these genes and their mutations appear to affect interactions with repair proteins substantially. Specific dietary consumption may lessen the detrimental effects of arsenic poisoning on protein function. We hypothesized that the mutations might be reversed by attaching particular molecules to these mutants. The protective effects of six curcumin compounds were examined using molecular docking with AutoDock 4.2.6 to assess protein dynamics and binding interactions. Optimal complexes were selected for dynamics simulation using GROMACS, and potential strategies for long-term cancer prevention related to arsenic exposure were identified.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148127862","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":"Copper Pyrithione Inhibits Trophoblast Cell Function: Mechanisms Underlying Its Embryotoxic Potential","authors":"Ziqin Lu,&nbsp;Xiangxue Cai,&nbsp;Xiumei Wang,&nbsp;Bingbing Luo,&nbsp;Junbiao Mao,&nbsp;Junling Wang","doi":"10.1002/em.70048","DOIUrl":"10.1002/em.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>Copper pyrithione (CuPT), a widely used antimicrobial agent in antifouling coatings and consumer products, has potential reproductive toxicity. This study aims to evaluate the impact of CuPT on human trophoblast-like JEG-3 cells and elucidate potential molecular mechanisms. Proliferation was assessed by CCK-8; migration and invasion by wound-healing and Matrigel Transwell assays; cell cycle and apoptosis by flow cytometry; intracellular reactive oxygen species (ROS) by DCFH-DA; DNA double-strand breaks by γ-H2AX immunofluorescence. Transcriptomic changes were profiled by RNA-seq with differential expression and GO enrichment analyses. Autophagy and endoplasmic reticulum (ER) stress markers were assessed by immunofluorescent staining. Key differentially expressed genes were validated by qRT–PCR. CuPT suppressed JEG-3 proliferation in a time- and concentration-dependent manner and reduced migratory and invasive capacities versus controls. Under 80 nM for 72 h, cell-cycle phase distribution showed no significant changes, but late apoptosis increased and intracellular ROS levels rose, indicating oxidative stress. γ-H2AX foci were elevated, consistent with DNA damage. RNA-seq revealed 648 upregulated and 451 downregulated genes, with enrichment of ER-stress, unfolded-protein response, intrinsic apoptotic signaling, and autophagy pathways among upregulated genes, and suppression of oxygen-response, glycolytic/energy metabolism, sterol biosynthesis, and cell-adhesion/mitotic regulation among downregulated genes. Concurrently, CuPT activated pronounced autophagosome formation and an ER stress response. CuPT treatment downregulated CYTB, ND6, and Egln3 expressions and upregulated NUPR1 and SQSTM1 expressions. CuPT impairs trophoblast-like JEG-3 cell proliferation, migration, and invasion, accompanied by increased ROS and DNA damage. Integrated RNA-seq and staining data indicate activation of ER stress and autophagy.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867285","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":"Analysis of Mutagenesis in the Escherichia coli tdk Gene: The Nucleoid Protein HNS Is Required for a Dramatic Cisplatin-Induced Hotspot","authors":"Dana Sorensen,&nbsp;Tara Mata,&nbsp;Ananya Sridharan,&nbsp;Mallika Mathew,&nbsp;Emily Sagastume,&nbsp;Natasha Sutkin,&nbsp;Katherine Douglas,&nbsp;Mila Daniel,&nbsp;Angela Hung,&nbsp;Alina Garmash,&nbsp;Annette Hsieh,&nbsp;Jamie Elizabeth Ortega,&nbsp;Jeffrey H. Miller","doi":"10.1002/em.70054","DOIUrl":"10.1002/em.70054","url":null,"abstract":"<p>We demonstrate the utility of the <i>tdk</i> reporter gene system, by showing its ability to not only analyze mutational hotspots, but also to allow the analysis of both weak and strong mutator or mutagen effects. It can detect large and small insertions and deletions, as well as base substitutions. We previously defined cisplatin (CPT)-induced hotspots in <i>tdk</i>. One extraordinary hotspot for G:C- &gt; T:A transversions at base pair (bp) 499 is in a region of the gene that appears to be mutationally prone, suggesting that the conformation of the DNA in that region may play a major role in elevating mutation rates. Here, we examined CPT-induced mutations in a derivative of the starting wild-type strain that lacks the nucleoid binding protein HNS, which is involved in the folding and compaction of the <i>E. coli</i> chromosome. In this strain background the extraordinary CPT-induced hotspot disappears, pinpointing the importance of DNA conformation in mutation rates at certain positions. We further show that this A:T-rich gene is a magnet for transposable elements.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Communication: Increased Frequency of Micronucleus in the Bone Marrow of Mice Under Simulated Occupational Exposure to Isoflurane","authors":"Marina Zanin,&nbsp;Mariana Gobbo Braz,&nbsp;Maria Vitória Destro,&nbsp;Antonio S. Varela Junior,&nbsp;Martielo Ivan Gehrcke,&nbsp;Carine Dahl Corcini","doi":"10.1002/em.70052","DOIUrl":"10.1002/em.70052","url":null,"abstract":"<p>Isoflurane is a widely used inhalational anesthetic. Occupational exposure to waste anesthetic gases (WAGs) raises concerns about DNA damage. Bone marrow, highly susceptible due to its proliferative activity, has been scarcely investigated in rodents after exposure to WAGs. Therefore, the present study evaluated the impact of this exposure on micronucleus (MN) frequency and cytotoxicity, under conditions that mimic work environments with WAG to which thousands of professionals worldwide are occupationally exposed. Swiss mice were randomized into control, exposed, and recovery groups. Animals were subjected to daily 5 h exposures to 50 ppm isoflurane for 30 days. Bone marrow samples were analyzed using the MN assay. Isoflurane-exposed mice showed a significant increase in micronucleated polychromatic erythrocytes compared to controls (<i>p</i> &lt; 0.0001). The recovery group exhibited a partial reduction after 20 days without exposure, though values remained above the control. Simulated occupational isoflurane exposure induces chromosomal instability in bone marrow cells, even at recommended safety levels.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative DNA Damage Exacerbates the Mutagenic Potential of Alternative DNA Structures via Altered DNA Repair Processing","authors":"Alex W. Klattenhoff,&nbsp;Maha Zewail-Foote,&nbsp;Arti Madan,&nbsp;Anna Chiu,&nbsp;Karen M. Vasquez","doi":"10.1002/em.70059","DOIUrl":"10.1002/em.70059","url":null,"abstract":"<p>Alternative DNA structure-forming (i.e., non-B) sequences such as H-DNA-forming sequences are enriched at chromosomal translocation hotspots in human cancer genomes, underscoring their role in genomic instability. H-DNA is particularly susceptible to DNA damage by reactive oxygen species (ROS), a common byproduct from both endogenous metabolism and environmental contaminants, thereby exacerbating its mutagenic potential. Oxidative lesions within B-DNA are efficiently processed by base excision repair (BER), whereas H-DNA is processed in a mutagenic fashion by nucleotide excision repair (NER). Thus, we speculate that the repair of oxidative lesions within H-DNA will promote aberrant BER and NER processing, ultimately enhancing mutagenesis. Here, we examine the processing of oxidative damage within H-DNA by measuring the changes in mutation frequencies and spectra, as well as the association with key NER and BER proteins in human cells in the presence or absence of specific DNA repair proteins. Our results demonstrate that oxidatively damaged H-DNA serves as a substrate for both BER and NER and reveals an interplay between BER and NER proteins, which influences mutation outcomes. This novel framework establishes a link between oxidative stress, DNA repair, and H-DNA-associated mutagenesis, providing insight into how environmentally relevant DNA damage can drive sequence-specific genomic instability at cancer-associated hotspots.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmark Response Values for Error-Corrected Sequencing Mutagenicity Assessment Technologies","authors":"Saron Mulugeta,&nbsp;Francesco Marchetti,&nbsp;Guangchao Chen,&nbsp;Connie Chen,&nbsp;Raechel Puglisi,&nbsp;Paul A. White","doi":"10.1002/em.70051","DOIUrl":"10.1002/em.70051","url":null,"abstract":"<p>The Benchmark Dose (BMD) approach is commonly used to determine Point-of-Departure (PoD) values for risk assessment and regulatory decision-making; however, choosing a suitable Benchmark Response (BMR) for continuous endpoints is a challenge. Earlier work established a BMR of 50% for selected in vivo mutagenicity endpoints (i.e., Transgenic Rodent and <i>Pig-a</i>). Error-corrected sequencing (ECS) technologies, such as Duplex Sequencing (DupSeq), Hawk-Seq, PECC-Seq, and PacBio HiFi, have emerged as powerful tools for mutagenicity assessment. This study applied and compared two approaches for defining BMR values for ECS technologies: the Effect Size (ES) theory of Slob (2017), and the one standard deviation approach of Zeller et al. (2017). A dose–response database of ECS studies was compiled to determine technology-specific within-group variance values (<i>var</i>) for BMR determination. Experimental factor influences on <i>var</i>, including species, rodent strain, administration route, application time, tissue type, tissue sampling time, and DNA fragmentation method, were examined; no significant influences were detected. The absence of covariate effects justified using typical, technology-specific <i>var</i> values for BMR determinations. Using these values, technology-specific BMRs were calculated as 27.7% for DupSeq, 16.6% for Hawk-Seq, and 23.3% for PECC-Seq. BMRs derived from negative control values were 22.6 to 28.8% for DupSeq, 5.6 to 13.8% for Hawk-Seq, 28.7 to 31.5% for PECC-Seq, and 9.5 to 22.8% for PacBio HiFi. These findings support adoption of a 30% BMR for in vivo ECS mutagenicity assessment technologies, providing a robust and consistent foundation for future dose–response modeling and human health risk assessment.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092475","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092474","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092477","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}