Environmental and Molecular Mutagenesis最新文献_第2页

Re-Evaluating Acceptable Intake: A Comparative Study of N-Nitrosomorpholine and N-Nitroso Reboxetine Potency 重新评估可接受的摄入量：n -亚硝基somorpholine和n -亚硝基Reboxetine效力的比较研究。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-03-22 DOI: 10.1002/em.70007

Shaofei Zhang, Jennifer Cheung, Jakub Kostal, Adelina Voutchkova-Kostal, Maik Schuler

{"title":"Re-Evaluating Acceptable Intake: A Comparative Study of N-Nitrosomorpholine and N-Nitroso Reboxetine Potency","authors":"Shaofei Zhang, Jennifer Cheung, Jakub Kostal, Adelina Voutchkova-Kostal, 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}

引用次数: 0

Extracellular Vesicle (EV) Mechanisms of Toxicity for Per and Polyfluoroalkyl Substances: Comparing Transcriptomic Points of Departure Across Global Versus EV Regulatory Gene Sets 细胞外囊泡（EV）对Per和多氟烷基物质的毒性机制：比较全球与EV调节基因集的转录组起点。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-03-19 DOI: 10.1002/em.70008

Celeste K. Carberry, Hadley Hartwell, Cynthia V. Rider, Matthew W. Wheeler, Scott S. Auerbach, Julia E. Rager

{"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, Hadley Hartwell, Cynthia V. Rider, Matthew W. Wheeler, Scott S. Auerbach, 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}

引用次数: 0

Mitigation of Volatile Chemicals' Effect on Adjacent Microtiter Plate Wells 降低挥发性化学物质对相邻微滴板孔的影响。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-03-13 DOI: 10.1002/em.70005

Svetlana L. Avlasevich, Erica Briggs, Kyle Tichenor, Adam Conrad, Nikki Hall, Steven M. Bryce, Jeffrey C. Bemis, Stephen D. Dertinger

{"title":"Mitigation of Volatile Chemicals' Effect on Adjacent Microtiter Plate Wells","authors":"Svetlana L. Avlasevich, Erica Briggs, Kyle Tichenor, Adam Conrad, Nikki Hall, Steven M. Bryce, Jeffrey C. Bemis, 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}

引用次数: 0

Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques 用出发点分析和ToxPi可视化技术合成多流分析的遗传毒性结果。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-03-13 DOI: 10.1002/em.70003

Yusuf Hussien, Stephen D. Dertinger, George E. Johnson

{"title":"Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques","authors":"Yusuf Hussien, Stephen D. Dertinger, 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}

引用次数: 0

Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines. 预测人类细胞系体外遗传毒性的转录组生物标志物综述。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-03-04 DOI: 10.1002/em.70004

Heng-Hong Li, Jiri Aubrecht, Tatyana Y Doktorova, Danyel Jennen, J Christopher Corton, Roland Froetschl, Roman Mezencev, Carole L Yauk

{"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}

引用次数: 0

Tong-man Ong (June 9, 1935–January 5, 2025) 王同文（1935 年 6 月 9 日-2025 年 1 月 5 日）。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-02-28 DOI: 10.1002/em.70001

Gopala Krishna

引用次数: 0

Characterizing the Pulmonary Toxicity and Potential Mutagenicity of Formaldehyde Fumes in a Human Bronchial Epithelial Tissue Model 在人支气管上皮组织模型中表征甲醛烟雾的肺毒性和潜在致突变性。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-02-24 DOI: 10.1002/em.70000

Yuan Le, Baiping Ren, Levan Muskhelishvili, Kelly Davis, Yiying Wang, William Gwinn, Diego Rua, Robert H. Heflich, Xuefei Cao

{"title":"Characterizing the Pulmonary Toxicity and Potential Mutagenicity of Formaldehyde Fumes in a Human Bronchial Epithelial Tissue Model","authors":"Yuan Le, Baiping Ren, Levan Muskhelishvili, Kelly Davis, Yiying Wang, William Gwinn, Diego Rua, Robert H. Heflich, Xuefei Cao","doi":"10.1002/em.70000","DOIUrl":"10.1002/em.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>Formaldehyde (FA) is a highly reactive aldehyde that is regarded as an inhalation hazard and human carcinogen. Herein, we report a follow-up study evaluating the effects of exposure duration on the toxicity and mutagenicity of FA using a human in vitro air-liquid-interface (ALI) airway tissue model. Previously we exposed ALI cultures to 7.5, 15 and 30-ppm FA fumes 4 h/day for 5 days; currently, we have increased the exposure duration of cultures exposed to 7.5 and 15 ppm FA to 5 days/week for 4 weeks, followed by a 28-day recovery. Due to its toxicity, cultures exposed to 30 ppm FA were treated for 5 days, followed by the recovery. Tissue responses were evaluated following the treatment and recovery. DNA damage was measured using the Comet-Chip assay after 3 days of exposure, and mutagenesis was evaluated by duplex sequencing following the recovery. The toxicity detected following the 4-week exposure was similar to that seen previously with the 5-day exposures: both 7.5 and 15 ppm FA induced moderate decreases in tissue integrity, FANCD2 DNA-repair enzyme expression and IL-6 release, and moderate increases in IL-1RA release. Effects on cell proliferation, ciliary function and tissue structure were minimal. Additionally, neither the 4-week exposure to 7.5 and 15 ppm FA nor the 5-day exposure to 30 ppm FA induced DNA damage or mutations. Using this experimental design, exposure of human ALI airway cultures to FA fumes does not produce genotoxicity or mutagenicity, even when exposures are conducted over a 28-day period.</p>\u0000 </div>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 1-2","pages":"6-21"},"PeriodicalIF":2.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482441","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}

引用次数: 0

Epigenetic Modifications Associated With Wildland–Urban Interface (WUI) Firefighting 与荒地-城市界面（WUI）灭火相关的表观遗传修饰。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-02-19 DOI: 10.1002/em.70002

Jaclyn M. Goodrich, Melissa A. Furlong, Derek J. Urwin, Jamie Gabriel, Jeff Hughes, Alesia M. Jung, Miriam M. Calkins, Kathleen N. DuBose, Alberto J. Caban-Martinez, Natasha Schaefer Solle, Shawn C. Beitel, Jefferey L. Burgess

{"title":"Epigenetic Modifications Associated With Wildland–Urban Interface (WUI) Firefighting","authors":"Jaclyn M. Goodrich, Melissa A. Furlong, Derek J. Urwin, Jamie Gabriel, Jeff Hughes, Alesia M. Jung, Miriam M. Calkins, Kathleen N. DuBose, Alberto J. Caban-Martinez, Natasha Schaefer Solle, Shawn C. Beitel, Jefferey L. Burgess","doi":"10.1002/em.70002","DOIUrl":"10.1002/em.70002","url":null,"abstract":"<p>Wildland–urban interface (WUI) firefighting involves exposure to burning vegetation, structures, and other human-made hazards, often without respiratory protection. Response activities can last for long periods of time, spanning multiple days or weeks. Epigenetic modifications, including microRNA (miRNA) expression and DNA methylation, are responsive to toxicant exposures and are part of the development of cancers and other diseases. Epigenetic modifications have not been studied in relation to WUI fires. Firefighters (<i>n</i> = 99) from southern California, including 79 firefighters who responded to at least one WUI fire, provided blood samples at baseline and approximately 10 months later. We quantified the relative abundance of 800 miRNAs in blood samples using the nCounter Human v3 miRNA expression panel and blood leukocyte DNA methylation throughout the genome via the Infinium EPIC array. We used linear mixed models to compare the expression of each miRNA across time and DNA methylation at each locus, adjusting for potential confounders. In the miRNA analysis among all firefighters, 65 miRNAs were significantly different at follow-up compared to baseline at a false discovery rate of 5%. Results were similar when restricted to firefighters with a recorded WUI fire exposure during the interim period, although only 50 were significant. Expression of miRNA hsa-miR-518c-3p, a tumor suppressor, was significantly associated with WUI fire response (fold change 0.77, 95% CI = [0.69, 0.87]). In the DNA methylation analysis, no statistically significant changes over time were identified. In summary, WUI fire exposures over a wildfire season altered miRNA expression but did not substantially impact DNA methylation.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 1-2","pages":"22-33"},"PeriodicalIF":2.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448588","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}

引用次数: 0

Review and meta-analysis of gene expression biomarkers predictive of chemical-induced genotoxicity in vivo. 基因表达生物标志物预测体内化学诱导的遗传毒性的综述和荟萃分析。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-01-21 DOI: 10.1002/em.22646

J Christopher Corton, Scott S Auerbach, Naoki Koyama, Roman Mezencev, Carole L Yauk, Takayoshi Suzuki

{"title":"Review and meta-analysis of gene expression biomarkers predictive of chemical-induced genotoxicity in vivo.","authors":"J Christopher Corton, Scott S Auerbach, Naoki Koyama, Roman Mezencev, Carole L Yauk, Takayoshi Suzuki","doi":"10.1002/em.22646","DOIUrl":"https://doi.org/10.1002/em.22646","url":null,"abstract":"<p><p>There is growing recognition across broad sectors of the toxicology community that gene expression biomarkers have the potential to identify genotoxic and nongenotoxic carcinogens through a weight-of-evidence approach, providing opportunities to reduce reliance on the 2-year bioassay to identify carcinogens. In August 2022, a workshop within the International Workshops on Genotoxicity Testing (IWGT) was held to critically review current methods to identify genotoxicants using various 'omics profiling methods. Here, we describe the findings of a workshop subgroup focused on the state of the science regarding the use of biomarkers to identify chemicals that act as genotoxicants in vivo. A total of 1341 papers were screened to identify those that were most relevant. While six published biomarkers with characterized accuracy were initially examined, four of the six were not considered further, because they had not been tested for classification accuracy using additional sets of chemicals or other transcript profiling platforms. Two independently derived biomarkers used in conjunction with standard computational techniques can identify genotoxic chemicals in vivo (rat liver or both rat and mouse liver) on different gene expression profiling platforms. The biomarkers have predictive accuracies of ≥92%. These biomarkers have the potential to be used in conjunction with other biomarkers in integrated test strategies using short-term rodent exposures to identify genotoxic and nongenotoxic chemicals that cause cancer.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002242","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}

引用次数: 0

Assessing the impact of different solvents in the bacterial reverse mutation test 评估不同溶剂对细菌反向突变试验的影响。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2025-01-13 DOI: 10.1002/em.22649

Satyam N. Patel, Chetan K. Kajavadara, Rushikesh M. Shukla, Darshan T. Valani, Laxit K. Bhatt, Rajesh Sundar, Mukul R. Jain

{"title":"Assessing the impact of different solvents in the bacterial reverse mutation test","authors":"Satyam N. Patel, Chetan K. Kajavadara, Rushikesh M. Shukla, Darshan T. Valani, Laxit K. Bhatt, Rajesh Sundar, Mukul R. Jain","doi":"10.1002/em.22649","DOIUrl":"10.1002/em.22649","url":null,"abstract":"<p>The bacterial reverse mutation test is essential for identifying the mutagenic potential of chemicals. The solubility of the test substance is vital for achieving the recommended assay concentration. Preferred solvents like dimethyl sulfoxide and water are chosen for their compatibility and historical data. Selecting a compatible solvent with <i>Salmonella typhimurium</i> and <i>Escherichia coli</i> WP2 uvrA strains, considering a maximum cytotoxic concentration or the limit of 5 mg/plate, can be challenging. This study assessed various solvents, including N,N-dimethylformamide, acetone, acetonitrile, ethyl acetate, 95% ethanol, diethylene glycol monomethyl ether, methanol, P-dioxane, tetrahydrofuran, and dimethylacetamide, as alternative solvents in the AMES test. Results showed all solvents, except tetrahydrofuran, were compatible at concentrations up to 100 μL/plate or more, as they did not inhibit S9 enzymes, bacterial growth, or alter bacterial revertant colony counts, making them suitable for the bacterial reverse mutation test.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 1-2","pages":"69-76"},"PeriodicalIF":2.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970184","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}

引用次数: 0