Environmental and Molecular Mutagenesis最新文献

{"title":"Conserved Active Site Loop Residues of E. coli DinB and Human DNA Polymerase Kappa Govern Activity","authors":"Nicole M. Antczak,&nbsp;Paul Ippoliti,&nbsp;Jiyoun Ahn,&nbsp;Lakindu Pathira Kankanamge,&nbsp;Tamara Dudko,&nbsp;Khadijah Balfour-Jeffrey,&nbsp;Bix Pancoe,&nbsp;Zoe MacDiarmid,&nbsp;Chuc May Pham,&nbsp;David Williams,&nbsp;Alexandra Mora,&nbsp;Jason M. Walsh,&nbsp;Penny J. Beuning","doi":"10.1002/em.70075","DOIUrl":"10.1002/em.70075","url":null,"abstract":"<p>DNA damage is ubiquitous and can arise from numerous sources. To mitigate the potential effects of DNA damage, cells possess varied DNA repair and damage tolerance mechanisms. Conserved throughout evolution, specialized DNA damage-bypass DNA polymerases from the Y family provide DNA damage tolerance. <i>E. coli</i> harbors two Y-family polymerases whereas humans have four members of the Y family. <i>E. coli</i> DinB and human DNA polymerase kappa have shown similar damage bypass profiles in that they both are specific for minor groove adducts and are inhibited by major groove adducts. These two proteins share a similar active site loop that is adjacent to the nascent base pair. These active site loops were analyzed by alanine scanning mutagenesis with the resulting proteins characterized in primer extension assays and for their thermal stability. Most variants show similar activity to the respective wild-type proteins, with a few mutations resulting in dramatic losses of activity and changes in stability. The effects of the mutations are remarkably similar in DinB and polymerase kappa, with mutation of specific aligned residues showing decreased activity and/or stability. Most of the variants have similar thermal stability as the respective wild-type proteins and show the characteristic increase in stability in the presence of substrates, with the less active variants in general showing limited stabilization by DNA or DNA and incoming nucleotides.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683735","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":"Investigation of Ethylene Oxide Genotoxicity Dose–Response to Inform Cancer Risk Assessment","authors":"B. Bhaskar Gollapudi,&nbsp;James E. Bus,&nbsp;Phillip Cassidy,&nbsp;Jeffrey T. Weinberg,&nbsp;Jeffrey C. Bemis,&nbsp;Dorothea K. Torous,&nbsp;Stephen D. Dertinger,&nbsp;Kun Lu,&nbsp;Richard Reiss,&nbsp;Abby A. Li","doi":"10.1002/em.70072","DOIUrl":"10.1002/em.70072","url":null,"abstract":"<p>Ethylene oxide (EtO) is primarily used as an intermediate in the manufacture of chemicals, with a minor use as a sterilant for medical equipment and food products. It is a direct-acting alkylating agent that reacts with cellular macromolecules, including proteins and DNA. EtO has been shown to induce tumors in rodents and humans. DNA reactivity has been the postulated mode of action (MOA) for its carcinogenicity. The current study has investigated the dose response for EtO-induced genetic damage to inform the biological plausibility of a dose–response model for cancer risk assessment. Male and female B6C3F1 mice (≥ 10/sex/concentration) were exposed to 0, 0.05, 0.1, 0.5, 1, 50, 100, or 200 ppm EtO by whole-body inhalation (6 h/day for 28 days, 7 days/week). Mutagenicity was assessed by determining the frequency of mutant <i>Pig-a</i> phenotype in reticulocytes (RET) and mature red blood cells (RBC) on Day 28. Cytogenetic damage was evaluated by the erythrocyte micronucleus (MN) test in blood samples collected on Days 5 and 28. EtO is a relatively weak genotoxicant with treatment-related increases in <i>Pig-a</i> and MN frequencies being seen primarily at 200 ppm. The hockey-stick shaped dose response for genetic damage may be conservatively interpreted as being no more than a linear response with a single slope. Thus, a cancer risk assessment dose–response model consisting of a single shallow linear slope throughout the exposure range is biologically plausible and consistent if EtO were acting through a mutagenic MoA for its carcinogenicity.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444408","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":"Evaluating the Suitability of HepaRG Cells for Regulatory Micronucleus Testing: Comparing Results for a Diverse Set of 28 Chemicals to Regulatory Accepted TK6 Cells","authors":"Ashley Allemang,&nbsp;Stefan Pfuhler","doi":"10.1002/em.70062","DOIUrl":"10.1002/em.70062","url":null,"abstract":"<p>There is growing interest in in vitro-based new approach methodologies (NAMs) for assessing genotoxicity. These approaches are desirable for industries like cosmetics which are prohibited from animal testing due to regulatory restrictions, as well as “3R” considerations to avoid in vivo testing. One NAM is the adaptation of the in vitro micronucleus assay for metabolically competent human hepatic HepaRG cells. However, per OECD Test Guideline 487, the use of non-validated cell types such as these needs to be justified based on their proficiency in the assay. To this end, we have tested 28 chemicals in HepaRG and TK6 human lymphoblast cells, a standard cell line considered validated for use in the in vitro micronucleus assay. HepaRG cells showed a high overall accuracy of 86%, compared to 75% for TK6 cells across a balanced set of expected in vivo positives and negatives across various genotoxic modes of action. The improved overall performance of HepaRG cells was predominantly based on their lower susceptibility towards compounds known to cause “false positive” responses (positive results in vitro, but are known to be negative in vivo), particularly those related to oxidative stress as demonstrated by the ToxTracker assay. The study indicates a high predictive capacity of HepaRG cells, suggesting that with further examination of chemicals requiring metabolic activation, they may be suitable for regulatory testing. These findings advocate for the incorporation of HepaRG cells into genotoxicity assessment frameworks, providing a more human-relevant approach that has the potential to improve risk assessment outcomes.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374922","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":"Resveratrol Mitigates Haloacetaldehyde Disinfection By-Products (HAL-DBPs)-Induced Oocyte Developmental Toxicity via Mitochondria-Dependent Pathways","authors":"Zaishan Yang,&nbsp;Sien Yao,&nbsp;Qimei Xu,&nbsp;Mengchan Li,&nbsp;Yongteng Zhang,&nbsp;Mianqun Zhang,&nbsp;Zhiguo Zhang,&nbsp;Zhaokang Cui,&nbsp;Mengting Wu,&nbsp;Yan Zou,&nbsp;Yang Gao,&nbsp;Yunhai Zhang,&nbsp;Huiqun Yin","doi":"10.1002/em.70070","DOIUrl":"10.1002/em.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>Haloacetaldehyde disinfection by-products (HAL-DBPs), a class of unregulated emerging contaminants formed during drinking water chlorination, are widely detected in the aquatic environment, yet their potential reproductive toxicity remains poorly understood. In this study, we used a chronic drinking water exposure model in mice (90 days) and subsequently evaluated oocyte developmental competence in vitro. A chronic drinking water exposure model with environmentally relevant concentrations of HAL-DBPs was established to systematically evaluate their effects on oocyte developmental competence and to investigate the protective role of the natural antioxidant resveratrol (RES). The results showed that HAL-DBPs exposure significantly reduced oocyte maturation rate and early embryonic development potential, leading to spindle disorganization, chromosomal misalignment, and disruption of the actin cytoskeleton. Moreover, HAL-DBPs induced mitochondrial membrane potential loss, lipid metabolic disorder, impaired autophagy-lysosomal flux, excessive ROS accumulation, DNA damage, and apoptosis. Notably, RES cotreatment markedly alleviated these adverse effects by restoring mitochondrial function and redox homeostasis, reducing DNA damage and apoptosis, and preserving cytoskeletal integrity. Collectively, this study provides the first evidence that HAL-DBPs directly impair female germ cells through mitochondria-dependent oxidative stress mechanisms and proposes RES as a promising natural antioxidant intervention to mitigate reproductive toxicity associated with drinking water disinfection by-products.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359947","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":"DZNep: A Methyltransferase Modulator for Disease Mitigation","authors":"Sarita Garg,&nbsp;Isabelle R. Miousse","doi":"10.1002/em.70071","DOIUrl":"10.1002/em.70071","url":null,"abstract":"<div>\u0000 \u0000 <p>While commonly described as an inhibitor of the histone methyltransferase EZH2, the compound 3-deazaneplanocin A (DZNep) functions as an inhibitor of S-adenosylhomocysteine hydrolase (SAHH), leading to pan-methyltransferase inhibition affecting over 150 individual enzyme targets. DZNep has been associated with significant benefits in limiting the development of multiple diseases in animal models. This review synthesizes evidence from preclinical studies demonstrating DZNep's therapeutic potential across multiple disease contexts. The compound shows particular promise as an anticancer and antifibrotic agent. DZNep exhibits consistent anti-inflammatory effects across diverse disease models. The compound shows a favorable safety profile at therapeutic doses, though comprehensive toxicology data remain limited to short-term animal studies. While some effects correlate with EZH2 inhibition, the breadth of DZNep's therapeutic activity suggests mechanisms extending beyond this single target. Clinical translation remains the critical next step for validating DZNep's potential and safety as a multi-target therapeutic agent capable of mitigating diverse pathological processes through methyltransferase modulation.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316374","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":"Transcriptional Dysregulation of Histone Methyltransferase Genes and Chromosomal Instability Associated With Chronic Pesticide Exposure","authors":"Renato Arthur Franco Rodrigues,&nbsp;Eduardo Vignoto Fernandes,&nbsp;Mayara Bocchi,&nbsp;Fermino Sanches Lizarte Neto,&nbsp;Fábio Morato de Oliveira","doi":"10.1002/em.70069","DOIUrl":"10.1002/em.70069","url":null,"abstract":"<div>\u0000 \u0000 <p>Occupational pesticide exposure is a significant environmental health concern associated with genomic instability. Histone methyltransferases including <i>SMYD2</i>, <i>SMYD3</i>, <i>EZH2</i>, and <i>SETD8</i> participate in chromatin regulation and DNA damage responses, but their transcriptional profiles in exposed populations remain poorly understood. To evaluate chromosomal instability and expression of histone methyltransferase genes in agricultural workers. A cross-sectional biomonitoring study included 137 participants classified as directly exposed (<i>n</i> = 62), indirectly exposed (<i>n</i> = 41), or putative non-exposed (<i>n</i> = 34). Buccal epithelial cells were collected for micronucleus (MN) analysis and gene expression profiling. Relative mRNA expression levels of <i>SMYD2</i>, <i>SMYD3</i>, <i>EZH2</i>, and <i>SETD8</i> were quantified by RT-qPCR. Statistical analyses included ANOVA, correlation analyses, and multivariable regression models. MN frequency increased significantly according to exposure status, with directly exposed workers exhibiting the highest levels of chromosomal damage (7.0 ± 1.2 MN/2000 cells), followed by indirectly exposed individuals (3.9 ± 1.0 MN/2000 cells) and putative non-exposed participants (2.1 ± 0.6 MN/2000 cells) (<i>p</i> &lt; 0.001). Consistent use of personal protective equipment was associated with lower MN frequencies among directly exposed workers (<i>p</i> &lt; 0.001). Gene expression analyses demonstrated increased <i>EZH2</i> and <i>SETD8</i> expression in exposed groups, whereas <i>SMYD3</i> exhibited greater transcriptional variability than <i>SMYD2</i>. Significant positive correlations between MN frequency and expression levels of <i>EZH2</i>, <i>SETD8</i>, <i>SMYD3</i>, and <i>SMYD2</i> were observed among directly exposed workers (all <i>p</i> &lt; 0.05). Chronic occupational pesticide exposure is associated with chromosomal instability and altered expression of genes involved in chromatin regulation. These findings support their utility as potential exposure biomarkers.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276622","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":"Evaluation of Type 1 Error Rates in Duplex Sequencing for Mutagenicity Testing Using Vehicle Control Data and Simulation Analyses","authors":"Andrew Williams,&nbsp;Shaofei Zhang,&nbsp;Dingzhou Li,&nbsp;Wen Sun,&nbsp;Maik J. Schuler,&nbsp;Francesco Marchetti,&nbsp;Carole L. Yauk","doi":"10.1002/em.70067","DOIUrl":"10.1002/em.70067","url":null,"abstract":"<p>Accurate mutation detection and quantification are crucial for understanding mutagenesis and its potential health implications. Traditional in vivo mutagenicity assays, such as the transgenic rodent gene mutation assay, are limited by their focus on single reporter genes and inability to efficiently generate mutation spectra. Error-corrected sequencing (ECS) technologies like Duplex Sequencing (DS) offer significant advantages, including extremely low error rates and the ability to measure mutation frequencies (MFs) across various tissues and model organisms. Before ECS approaches can be adopted for regulatory purposes, their performance characteristics, particularly the type 1 error rate, must be rigorously established. We evaluated the type 1 error rate of DS through empirical analysis of vehicle control data and complementary simulation studies. Using 138 control mouse liver samples from 28 studies analyzed with the TwinStrand Mouse Mutagenesis Panel, we performed variance component analysis and found that experiment-level variability exceeds within-experiment sample variability. To evaluate the impact of between-study heterogeneity, we simulated overdispersed binomial data informed by the observed variance components. Removing the most variable studies reduced overdispersion and improved control of the type 1 error rate. Our findings demonstrate that DS maintains appropriate type 1 error rates (~0.05) when study heterogeneity is limited and at least four samples per group are used. Under greater overdispersion, sample sizes of five or six per group may be needed to achieve comparable control of the type 1 error rate. These results underscore the importance of combining empirical and simulation-based approaches to evaluate and optimize the statistical performance of emerging genomic technologies.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263632","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":"Benzo[b]fluoranthene Induces Mutation Accumulation and Cancer-Relevant Mutational Signatures in Mouse Lung Alongside Steady State Levels of Chromosome Damage in Blood","authors":"Xinwen Zhang,&nbsp;Cheryl A. Hobbs,&nbsp;Miriam V. Rivas,&nbsp;Alex Diesing,&nbsp;Danielle P. M. LeBlanc,&nbsp;Gu Zhou,&nbsp;Julie F. Foley,&nbsp;Paul A. White,&nbsp;Francesco Marchetti,&nbsp;Carole L. Yauk,&nbsp;Stephanie L. Smith-Roe","doi":"10.1002/em.70063","DOIUrl":"10.1002/em.70063","url":null,"abstract":"<p>Polycyclic aromatic hydrocarbons (PAHs) are well-known for their mutagenic and carcinogenic effects. Benzo[<i>b</i>]fluoranthene (BbF) is one of 16 PAHs prioritized by the US Environmental Protection Agency for toxicological evaluation due to pervasive human exposure. As part of a multi-stakeholder consortium, the genotoxic effects of BbF were evaluated in MutaMouse males exposed to five doses of BbF or a vehicle control via repeated oral gavage for 28, 60, 90, 120, or 180 days, with dose ranges adjusted by duration of exposure. Mutagenesis was evaluated in lung tissue (<i>n</i> = 4) at 28, 90, and 180 days using Duplex Sequencing (DS), and chromosomal damage (<i>n</i> = 8) was evaluated using the micronucleus assay in peripheral blood at all time points. Dose- and time-dependent increases in total mutation frequency (MF) and C:G &gt; A:T mutations were observed in lung tissue after 28, 90, and 180 days of exposure. By 28 days, BbF exposure produced lung cancer-associated mutational signatures linked to tobacco smoking. Mutations accumulated over time in lung, whereas chromosomal damage in peripheral blood erythrocytes reached a steady state by 28 days. Benchmark dose (BMD) confidence intervals (CIs) narrowed with extended exposure only for MF. Collectively, the data demonstrate that BbF is a potent mutagen capable of inducing cancer-relevant mutations in lung, supporting its potential role in human lung carcinogenesis. By distinguishing early mutagenic responses from cumulative mutation effects over time, these findings highlight the value of integrating mutagenicity assessment into extended-duration studies to better inform the potential health effects of chronic genotoxic exposures.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224085","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":"Multi-Omics Integration Into Adverse Outcome Pathway Framework: Principles, Progress, and Prospects for Next-Generation Toxicological Risk Assessment","authors":"Rajesh Pamanji,&nbsp;Ragothaman Prathiviraj,&nbsp;Gisha Sivan","doi":"10.1002/em.70068","DOIUrl":"10.1002/em.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>The adverse outcome pathway (AOP) framework has emerged as an important tool in mechanistic toxicology, providing chemically agnostic representations of the causal biological sequence from molecular initiating events (MIEs) to apical adverse outcomes (AOs). Yet, traditional AOP construction has relied predominantly on siloed, single-layer biological data, limiting both the mechanistic resolution and quantitative utility of AOPs in regulatory risk assessment. The proliferation of multi-omics technologies, such as transcriptomics, proteomics, metabolomics, and epigenomics, and their single-cell counterparts, now offers new opportunities to populate, validate, and quantify AOP networks with rich, multi-scale molecular data. This review systematically examines how each omics layer contributes uniquely to AOP development and discusses emerging frameworks for their integration. We describe the mechanistic logic underpinning transcriptome-guided key event (KE) identification, proteomic confirmation of KE-to-KE relationships (KERs), metabolomics-based linkage to phenotypic outcomes, epigenomic annotation of persistent and transgenerational effects, and single-cell resolution approaches that dissolve the cell population averaging problem inherent in bulk assays. We further assess quantitative AOP (qAOP) strategies built on benchmark dose (BMD) modeling of omics data, with emerging evidence that transcriptomic points of departure (tPODs) derived from short-term exposures are concordant with chronic apical endpoints. Critical knowledge gaps are identified, including incomplete molecular annotation of KEs in AOP-Wiki, the absence of standardized multiomics bioinformatics pipelines, the underdevelopment of epigenomic and spatial transcriptomic AOP layers, and regulatory hurdles impeding the translation of omics-derived PODs into health-based guidance values (HBGVs). We conclude with a forward-looking framework and research priorities to accelerate the regulatory acceptance of multiomics-informed AOPs as tools for next-generation chemical risk assessment.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 5-7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148865","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":"Histopathological and Epigenetic Insights Into Radioprotective Effects of Homeopathic Cadmium Sulfuratum in Swiss Albino Mice","authors":"Bekir Eren Çetin,&nbsp;Seda Ekici,&nbsp;Yasin Ozkabadayi,&nbsp;Hüsamettin Ekici","doi":"10.1002/em.70053","DOIUrl":"https://doi.org/10.1002/em.70053","url":null,"abstract":"<div>\u0000 \u0000 <p>Epigenetic mechanisms regulating DNA gene expression have gained significant attention in recent years. MicroRNAs (miRNAs) play a key role in these mechanisms by modulating gene activity and relaying information throughout the body. This study investigates the potential of a radioprotective homeopathic solution, ultra-diluted Cadmium Sulfuratum (UCS), to mitigate the acute side effects of radiotherapy by modulating miRNA expression. Radiotherapy, a crucial cancer treatment, unavoidably exposes normal tissues to radiation, often causing acute side effects such as bone marrow suppression and enteritis, which can lead to severe clinical conditions. Emerging evidence suggests that miRNAs can serve as biomarkers for predicting radiation-induced side effects before histopathological changes occur. This study investigated the histopathological effects of UCS on intestinal tissues and its impact on serum miRNA expression in Swiss albino mice exposed to total body irradiation (TBI) at 8 Gy. Specifically, seven miRNAs previously validated as biodosimeters were analyzed using quantitative PCR (qPCR) on the 2nd and sixth days post-irradiation. Additionally, histopathological and immunohistochemical analyses were conducted on intestinal epithelial cells. Our results revealed that UCS application significantly altered the expression levels of miRNAs, including mmu-miR-150-5p, mmu-mir-320a-5p, mmu-mir-200b-5p, mmu-mir-30a-5p, and mmu-miR-29a-5p, compared to radiation-only groups. Histopathological evaluations demonstrated that UCS reduced radiation-induced damage to intestinal epithelial cells. In conclusion, UCS exhibited radioprotective properties by modulating miRNA expression and alleviating acute radiation-induced intestinal damage. These findings highlight the potential of UCS in epigenetic modulation and its application in mitigating the side effects of radiotherapy, providing a foundation for future clinical research.</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":"148127861","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}