Environmental and Molecular Mutagenesis最新文献

{"title":"Aflatoxin B1-Induced Hepatic Mutagenesis in Mice Expressing Gene-Edited Neil1","authors":"Irina G. Minko,&nbsp;Vladimir L. Vartanian,&nbsp;Michael M. Luzadder,&nbsp;Yingming Wang,&nbsp;Lev M. Fedorov,&nbsp;Amanda K. McCullough,&nbsp;R. Stephen Lloyd","doi":"10.1002/em.70014","DOIUrl":"10.1002/em.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-associated mortality, correlating with obesity, alcohol consumption, hepatitis B and C infections, and dietary exposure to aflatoxin B₁ (AFB₁). The etiology of AFB₁-induced HCC involves the formation of highly mutagenic guanine lesions that can be repaired by a branch of the base excision repair pathway initiated by the DNA glycosylase, NEIL1. In a murine model, NEIL1 deficiency results in increased AFB₁-induced mutagenesis and carcinogenesis. Previous analyses identified several defective NEIL1 variants in human populations, including the temperature-sensitive A51V and glycosylase-deficient G83D variants. Herein, we report AFB₁-induced mutagenesis in mice expressing the A51V and G83D NEIL1 variants. Cohorts of 6-day-old <i>Neil1</i>^<i>A51V</i> and <i>Neil1</i>^<i>G83D</i> homozygous mice were injected with a single dose of AFB₁, and frequencies and spectra of mutations were assessed in liver genomes 2.5 months post-exposure using duplex sequencing. Comparisons of these data with previously generated data on AFB₁-induced mutagenesis in wild-type (WT) and <i>Neil1</i>^{<i>−/−</i>} mice revealed that although mutation frequencies in <i>Neil1</i>^<i>A51V</i> and <i>Neil1</i>^<i>G83D</i> animals were comparable to those measured in WT, elevated proportions of base substitutions at A/T sites were consistent with NEIL1 deficiency in both of these models. These findings suggest that individuals carrying these NEIL1 variants could be at an elevated risk for the development of AFB₁-induced HCC.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 4","pages":"144-154"},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987432","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":"Using N-Nitrosodiethanolamine (NDELA) and N-Nitrosopiperidine (NPIP) Transgenic Rodent Gene Mutation Data and Quantum Mechanical Modeling to Derive Potency-Based Acceptable Intakes for NDSRIs Lacking Robust Carcinogenicity Data","authors":"Jason M. Roper,&nbsp;Troy R. Griffin,&nbsp;George E. Johnson,&nbsp;Jakub Kostal,&nbsp;Raphael Nudelman,&nbsp;Gregory R. Ott,&nbsp;Adelina Voutchkova-Kostal,&nbsp;Valerie Niddam-Hildesheim","doi":"10.1002/em.70012","DOIUrl":"10.1002/em.70012","url":null,"abstract":"<div>\u0000 \u0000 <p>Acceptable intake (AI) limits for nitrosamine drug substance related impurities (NDSRIs) that lack carcinogenicity data could be estimated from mutagenic potency relative to anchor nitrosamines with carcinogenicity data. This approach integrates points of departure (PoDs) derived from in vivo mutagenicity studies with in silico predictions generated by a validated quantum-mechanical (QM) model. <i>N</i>-nitrosodiethanolamine (NDELA) and <i>N</i>-nitrosopiperidine (NPIP), with AIs derived from robust carcinogenicity data, were tested in the transgenic rodent (TGR) gene mutation assay. Liver mutant frequency and benchmark dose (BMD) modeling provided a suitable, robust, and precise PoD metric. BMD confidence intervals (CIs) calculated from mutant frequency expanded the potency range of previously reported BMD CIs for other anchor nitrosamines. Cancer-protective AIs for mutagenic NDSRIs can be pragmatically calculated on a potency basis by comparing their lower bound TGR BMD CIs with the BMD CIs and AIs derived from model/anchor nitrosamines that have results for in vivo gene mutation and cancer bioassays. In vivo modeling was supported by the Computer-Aided Discovery and RE-design (CADRE) program, a validated QM model for predicting NDSRI carcinogenic potency based on the underlying mechanism of mutagenicity. CADRE distinguished between anchor nitrosamines <i>N</i>-nitrosodiethylamine (NDEA) and <i>N</i>-nitrosodimethylamine (NDMA) and the less potent NDELA and NPIP. Scrutiny of underlying reactivity indices and relevant physicochemical properties rationalized the observed trend in metabolic activity and thus predicted carcinogenic potency. Leveraging the in vivo–in silico approach is valuable in gaining confidence in the proposed AIs, whereby the QM model serves as mechanistic validation of in vivo results.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 4","pages":"155-171"},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003967","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":"Benchmark Response (BMR) Values for In Vivo Mutagenicity Endpoints","authors":"Paul A. White,&nbsp;Guangchao Chen,&nbsp;Nikolai Chepelev,&nbsp;Madison A. Bell,&nbsp;Lauren R. Gallant,&nbsp;George E. Johnson,&nbsp;Andreas Zeller,&nbsp;Marc A. Beal,&nbsp;Alexandra S. Long","doi":"10.1002/em.70006","DOIUrl":"10.1002/em.70006","url":null,"abstract":"<p>The benchmark dose (BMD) approach constitutes the most effective and pragmatic strategy for the derivation of a point of departure (PoD) for comparative potency analysis, risk assessment, and regulatory decision-making. There is considerable controversy regarding the most appropriate benchmark response (BMR) for genotoxicity endpoints. This work employed the Slob (2017) Effect Size (ES) theory to define robust BMR values for the in vivo transgenic rodent (TGR) and <i>Pig-a</i> mutagenicity endpoints. An extensive database of dose–response data was prepared and curated; BMD analyses were used to determine endpoint-specific maxima (i.e., parameter <i>c</i>) and within-group variance (i.e., <i>var</i>). Detailed analyses investigated the dependence of <i>var</i> on experimental factors such as tissue, administration route, treatment duration, and post-exposure tissue sampling time. The overall lack of influence of these experimental factors on <i>var</i> permitted the determination of typical values for the endpoints investigated. Typical <i>var</i> for the TGR endpoint is 0.19; the value for the <i>Pig-a</i> endpoint is 0.29. Endpoint-specific <i>var</i> values were used to calculate endpoint-specific BMR values; the values are 47% for TGR and 60% for <i>Pig-a</i>. Endpoint-specific BMR values were also calculated using the trimmed distribution of study-specific standard deviation (SD) values for concurrent controls. Those analyses yielded endpoint-specific BMR values for the TGR and <i>Pig-a</i> endpoints of 33% and 58%, respectively. Considering the results obtained, and the in vivo genetic toxicity BMR values noted in the literature, we recommend a BMR of 50% for in vivo mutagenicity endpoints. The value can be employed to interpret mutagenicity dose–response data in a risk assessment context.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 4","pages":"172-184"},"PeriodicalIF":2.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788162","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":"An Enhanced Metabolization Protocol for In Vitro Genotoxicity Assessment of N-Nitrosamines in Mammalian Cells","authors":"M. E. Geijer,&nbsp;A. M. Gernaat,&nbsp;N. Moelijker,&nbsp;I. Brandsma,&nbsp;G. Hendriks","doi":"10.1002/em.70009","DOIUrl":"10.1002/em.70009","url":null,"abstract":"<p>N-Nitrosamines (NAs) are probable human carcinogens and were detected as impurities in pharmaceuticals, which led to a concern for human health. NAs require metabolic activation before they become mutagenic, and not all NAs are mutagenic since their reactivity is related to their structure. While some NAs are potent mutagens in vivo, in vitro metabolization with exogenous S9 liver extract is generally less efficient. While an enhanced bacterial mutagenicity protocol was recently developed, which uses increased concentrations of S9 liver extracts, there presently is not an improved metabolization protocol suitable for mammalian cell genotoxicity assays. Therefore, we optimized a hamster S9 liver extract-based protocol for in vitro NA metabolization and assessed the genotoxic potential of various NAs using ToxTracker. With this enhanced metabolization protocol (EMP), the genotoxic potency of N-nitrosodimethylamine (NDMA) increased approximately 200-fold compared with the standard S9 liver extract-based exposure protocol in ToxTracker. The EMP was further validated with seven additional mutagenic NAs to which humans are commonly exposed: N-nitrosodiethylamine (NDEA), N-nitrosodiethanolamine (NDELA), N-nitrosodibutylamine (NDBA), N-nitrosofluoxetine (NF), 1-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), and 1-cyclopentyl-4-nitrosopiperazine (CPNP), and two non-mutagenic NAs: N-nitrosobupropion (NBuPRO) and N-nitrosoproline (NPRO). Genotoxicity could be confirmed for six NAs using the EMP, demonstrating that mammalian cells and the new approach methodology (NAM) ToxTracker may have potential when investigating NA-related genotoxicity.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 4","pages":"210-220"},"PeriodicalIF":2.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728764","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":"Re-Evaluating Acceptable Intake: A Comparative Study of N-Nitrosomorpholine and N-Nitroso Reboxetine Potency","authors":"Shaofei Zhang,&nbsp;Jennifer Cheung,&nbsp;Jakub Kostal,&nbsp;Adelina Voutchkova-Kostal,&nbsp;Maik Schuler","doi":"10.1002/em.70007","DOIUrl":"10.1002/em.70007","url":null,"abstract":"<p>Establishing regulatory limits for Drug Substance-Related Impurities (NDSRIs) is challenging due to the limited genotoxicity and carcinogenicity data available for many of these impurities, often leading to conservative approaches. In this study, we evaluated the genotoxic potential of two structurally related nitrosamines: N-nitrosomorpholine (NMOR) and N-nitroso reboxetine. Compared to the well-studied NMOR, there is little toxicological information available for N-nitroso reboxetine. Currently, both compounds have an acceptable intake value of 127 ng/day, based on a read-across using the available carcinogenicity data of NMOR. While both compounds tested positive in a series of in vitro and in vivo assays, we found that the mutagenic potential of N-nitroso reboxetine was significantly lower than that of NMOR. The benchmark dose (BMD) analysis of in vivo mutagenicity data supports an acceptable intake of 24,000 ng/day for N-nitroso reboxetine. Computational studies, carried out using the quantum-mechanical CADRE program, were consistent with in vitro and in vivo outcomes, suggesting an acceptable intake at or above 1500 ng/day for N-nitroso reboxetine. In comparison to NMOR, this prediction is supported by lower computed reactivity in the hydroxylation step, greater steric hindrance of the alpha carbons, and more facile proton transfer in the heterolysis toward the aldehyde metabolite. The data presented in this work can be used to refine and improve the Carcinogenic Potency Categorization Approach (CPCA). It also underscores the importance of collaboration between regulatory authorities, the pharmaceutical industry, and scientific researchers to address potential risks while avoiding overestimation of the acceptable intake limits for certain NDSRIs.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 3","pages":"80-98"},"PeriodicalIF":2.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676595","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":"Extracellular Vesicle (EV) Mechanisms of Toxicity for Per and Polyfluoroalkyl Substances: Comparing Transcriptomic Points of Departure Across Global Versus EV Regulatory Gene Sets","authors":"Celeste K. Carberry,&nbsp;Hadley Hartwell,&nbsp;Cynthia V. Rider,&nbsp;Matthew W. Wheeler,&nbsp;Scott S. Auerbach,&nbsp;Julia E. Rager","doi":"10.1002/em.70008","DOIUrl":"10.1002/em.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Extracellular vesicles (EVs) are emitted from cells throughout the body and serve as signaling molecules that mediate disease development. Emerging evidence suggests that per- and polyfluoroalkyl substances (PFAS) impact EV release and content, influencing liver toxicity. Still, the upstream regulators of EV changes affected by PFAS exposure remain unclear. This study evaluated the hypothesis that PFAS exposures, individually and in a mixture, alter the expression of genes involved in EV regulation at concentrations comparable to genes involved in global biological response mechanisms. HepG2 liver cells were treated at multiple concentrations with individual PFOS, PFOA, or PFHxA, in addition to an equimolar PFAS mixture. Gene expression data were analyzed using three pipelines for concentration-response modeling, with results compared against empirically derived datasets. Final benchmark concentration (BMC) modeling was conducted via Laplace model averaging in BMDExpress (v3). BMCs were derived at an individual gene level and across different gene sets, including Gene Ontology (GO) annotations as well as a custom EV regulation gene set. To determine relative PFAS contributions to the evaluated mixture, relative potency factors were calculated across resulting BMCs using PFOS as a standard reference chemical. Results demonstrated that PFAS exposures altered the expression of genes involved in EV regulation, particularly for genes overlapping with endoplasmic reticulum stress. EV regulatory gene changes occurred at similar BMCs as global gene set alterations, supporting concurrent regulation and the role of EVs in PFAS toxicology. This application of transcriptomics-based BMC modeling further validates its utility in capturing both established and novel pathways of toxicity.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 3","pages":"99-121"},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656519","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":"Mitigation of Volatile Chemicals' Effect on Adjacent Microtiter Plate Wells","authors":"Svetlana L. Avlasevich,&nbsp;Erica Briggs,&nbsp;Kyle Tichenor,&nbsp;Adam Conrad,&nbsp;Nikki Hall,&nbsp;Steven M. Bryce,&nbsp;Jeffrey C. Bemis,&nbsp;Stephen D. Dertinger","doi":"10.1002/em.70005","DOIUrl":"10.1002/em.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>In vitro new approach methodologies used to assess chemicals for biological effects are typically designed to limit the amount of test article required and to promote efficiencies such as compatibility with liquid handlers, and so forth. This is certainly true in the case of genetic toxicology, where many methods have been and continue to be developed with 96- or 384-well plate processing in mind. However, one recognized concern with microwell plates is that the volatility of test substances and/or their metabolites and/or their degradation products may affect adjacent wells. Here, we describe an approach that combines breathable membranes as well as activated carbon filters to mitigate volatility issues in 96 well plates. These experiments were performed with cyclophosphamide- and trimethylhydroquinone-exposed TK6 cells and utilized the biomarkers micronuclei, p53, γH2AX, phospho-histone H3, and nuclei to counting bead ratios to both demonstrate volatility impact and to assess the effectiveness of the solution described herein.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 3","pages":"134-141"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623939","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":"Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques","authors":"Yusuf Hussien,&nbsp;Stephen D. Dertinger,&nbsp;George E. Johnson","doi":"10.1002/em.70003","DOIUrl":"10.1002/em.70003","url":null,"abstract":"<p>In vitro genotoxicity has historically served a hazard identification role, with simple binary outcomes provided for each of several single endpoint assays. This will need to change, given: (i) efforts to curtail animal testing, (ii) the increased use of multiplexed in vitro assays and the ongoing development of NAMS, and (iii) the desire to holistically consider quantitative results from multiple biomarkers/endpoints that take potency into consideration. To help facilitate more quantitative analyses of multiple biomarkers and/or assay streams, we explored the combined use of PROAST and Toxicological Prioritization Index (ToxPi) software. As a proofofconcept, this investigation employed the MultiFlow DNA damage assay, focusing on γH2AX and p53 biomarkers at two time points, whereby 10 genotoxicants were evaluated in the presence and absence of rat liver S9 metabolic activation. Whereas PROAST was used to calculate BMD point estimates and confidence intervals (CIs), ToxPi synthesized the BMD results into visual, quantitative summaries conveying genotoxicity and metabolic properties. Our analyses suggest that ToxPi's data synthesis and visualization modules provide useful insights into compound response, chemical grouping, and genotoxic mechanisms. By integrating multiple data sources, we find that ToxPi offers a powerful complementary approach to traditional BMD CI graphs, particularly for the simultaneous analysis of multiple biomarkers, enhancing chemical potency analysis of complex datasets.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 3","pages":"122-133"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623941","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":"Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines.","authors":"Heng-Hong Li, Jiri Aubrecht, Tatyana Y Doktorova, Danyel Jennen, J Christopher Corton, Roland Froetschl, Roman Mezencev, Carole L Yauk","doi":"10.1002/em.70004","DOIUrl":"https://doi.org/10.1002/em.70004","url":null,"abstract":"<p><p>The current genotoxicity testing paradigm provides little mechanistic information, has poor specificity in predicting carcinogenicity in humans, and is not suited to assessing a large number of chemicals. Genomic technologies enable the characterization of genome-wide transcriptional changes in response to chemical treatments that can inform mechanisms or modes of action. These technologies provided an impetus to develop transcriptomic biomarkers that could transform genotoxicity hazard assessment for drugs, cosmetics, and environmental and industrial chemicals. In August 2022, the International Workshops on Genotoxicity Testing (IWGT) held a workshop to critically review progress in the development and application of transcriptomic biomarkers in genotoxicity testing. Here, we describe the findings of this workshop's subgroup that conducted a systematized review and analysis of in vitro transcriptomic biomarkers for evaluating genotoxicity. Although there is a multitude of published reports exploring transcriptomics in genetic toxicology, the working group identified only five in vitro transcriptomic biomarker candidates, of which three (GENOMARK, TGx-DDI, and MU2012) were independently developed with sufficiently defined context of use, validation data, and supporting case studies that warranted inclusion in the review. Although these in vitro biomarkers were developed independently and for different classes of chemicals (TGx-DDI for pharmaceuticals, GENOMARK for cosmetics, and MU2012 for medical and environmental chemicals), they all address the same shortfall of the standard in vitro genotoxicity testing battery, that is, lack of specificity by genotoxicity-induced stress response at the transcriptomic level. In this review, we discuss the development of these in vitro biomarkers, including challenges and progress toward achieving regulatory acceptance.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540637","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":"Tong-man Ong (June 9, 1935–January 5, 2025)","authors":"Gopala Krishna","doi":"10.1002/em.70001","DOIUrl":"10.1002/em.70001","url":null,"abstract":"","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 1-2","pages":"4-5"},"PeriodicalIF":2.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531300","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}