Environmental and Molecular Mutagenesis最新文献_第10页

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 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.\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":"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 (n = 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.","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}

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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":"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 Salmonella typhimurium and Escherichia coli 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.","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

Machine learning enhances genotoxicity assessment using MultiFlow® DNA damage assay 机器学习增强遗传毒性评估使用MultiFlow®DNA损伤分析。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2024-12-30 DOI: 10.1002/em.22648

Panuwat Trairatphisan, Lena Dorsheimer, Peter Monecke, Jan Wenzel, Rubin James, Andreas Czich, Yasmin Dietz-Baum, Friedemann Schmidt

{"title":"Machine learning enhances genotoxicity assessment using MultiFlow® DNA damage assay","authors":"Panuwat Trairatphisan, Lena Dorsheimer, Peter Monecke, Jan Wenzel, Rubin James, Andreas Czich, Yasmin Dietz-Baum, Friedemann Schmidt","doi":"10.1002/em.22648","DOIUrl":"10.1002/em.22648","url":null,"abstract":"Genotoxicity is a critical determinant for assessing the safety of pharmaceutical drugs, their metabolites, and impurities. Among genotoxicity tests, mechanistic assays such as the MultiFlow® DNA damage assay (MFA) allows the investigations on mode of action (MoA) of DNA damage through four mechanistic markers recorded at two time points. Previous studies have shown that machine learning (ML) can enhance precision on classifying the MoA of genotoxicants. Nevertheless, these approaches need to be tailored to specific chemical spaces and lab conditions for accurate risk assessment. In this study, we applied various state-of-the-art ML algorithms available in an open-source R package (caret) to build MFA-ML models using data from Bryce et al. (2016). The best model achieved 95% accuracy on the training dataset and correctly predicted genotoxicity in 16 out of 17 cases in the test dataset. Incorporating molecular descriptors properties from established in silico models demonstrated further improved performance of the approach to cover challenging examples of pharmaceuticals exhibiting a pharmacological mode of action that could interfere with the biomarker response. Further model validation on an external test set with 49 non-overlapped compounds showed a high model accuracy at 92%. Additionally, a tailored graphical user interface was developed using a freely available R package (shiny) to support visual analysis of MFA data including MoA predictions, facilitating broad usage by laboratory scientists. Lastly, a perspective on the integration of MoA predictions as additional evidence into a genotoxicity assessment workflow is proposed.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 1-2","pages":"45-57"},"PeriodicalIF":2.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909408","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

Genetic instability of a single exposure to sevoflurane at different concentrations in monitored mice 被监测小鼠单次接触不同浓度七氟醚的遗传不稳定性。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2024-12-26 DOI: 10.1002/em.22647

Maria Vitória Destro, Mariane A. P. Silva, Tony F. Grassi, Lídia R. de Carvalho, Daisy M. F. Salvadori, Leandro G. Braz, Mariana G. Braz

{"title":"Genetic instability of a single exposure to sevoflurane at different concentrations in monitored mice","authors":"Maria Vitória Destro, Mariane A. P. Silva, Tony F. Grassi, Lídia R. de Carvalho, Daisy M. F. Salvadori, Leandro G. Braz, Mariana G. Braz","doi":"10.1002/em.22647","DOIUrl":"10.1002/em.22647","url":null,"abstract":"Sevoflurane is an inhalation anesthetic widely used for general anesthesia, but its genotoxic potential is controversial in clinical studies. It is unknown whether the effects are due to surgery or the anesthetic. Thus, for the first time, the present study investigated genotoxicity in peripheral blood cells and in target organs (liver, lung, and kidney) and micronucleus (MN) in the bone marrow of a single exposure to sevoflurane at three different concentrations in monitored mice. Ninety Swiss mice were distributed into the following groups: exposure to sevoflurane at 3.3% (low), 4.5% (intermediate), and 6.0% (high) in 40% oxygen (O2) for 2 h; negative control (no exposure); negative control with O2; and positive control. The exposed animals were heated, monitored for vital signs (temperature, O2 saturation, heart rate/pulse, and respiratory rate), and anesthetized via a modern low-flow digital system. Mice were euthanized 2 and 24 h after exposure for evaluation by the comet assay and MN test, respectively. No DNA damage occurred in the 3.3% group for any of the organs evaluated, and no genotoxic or mutagenic effects were observed at any sevoflurane concentration in the peripheral blood or liver cells. However, a significant increase in DNA damage was observed at higher concentrations in kidney (4.5%) and lung cells (6.0%) and in the MN frequency (groups 4.5% and 6.0%). No cytotoxicity or histological alterations were observed. In conclusion, high concentrations of sevoflurane induce DNA damage, but concentrations equivalent to those used in clinical practice do not demonstrate genotoxic or mutagenic effects.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 1-2","pages":"58-68"},"PeriodicalIF":2.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893059","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

Hollaender award 2023: Adventures in applied genetic toxicology 2023 年霍兰德奖：应用遗传毒理学探险。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2024-11-27 DOI: 10.1002/em.22642

Rosalie K. Elespuru

{"title":"Hollaender award 2023: Adventures in applied genetic toxicology","authors":"Rosalie K. Elespuru","doi":"10.1002/em.22642","DOIUrl":"10.1002/em.22642","url":null,"abstract":"This work describes career “adventures” into applied research in environmental mutagenesis. Surprising and interesting results, as well as publications in Nature and Science, may counter an assumption that applied research is not as exciting or impactful as basic research. The narrative is described in terms of “mentors,” whose advice had a lasting impact and resonated in many ways. Adventures included forays into nitrosamine mutagenicity, nanomaterial assessment, photoactivated DNA damaging agents, p53 gene mutagenicity, germ cell mutagenic risk, bacterial mutagenicity assays, genotoxicity of cell phone radiation, Covid diagnostic PCR assays, personalized cancer prevention, and >25 years in regulatory safety assessment at FDA. FDA work included review of genotoxicity data, experiments in the lab, international standards generation, and collaboration with others to foster better analyses of DNA damaging agents, generally in relation to cancer risk. As demonstrated by accidental adventures that led to scientific as well as life-altering personal realizations, many of the most critical happenings in science and in life turn out to be “random,” unexpected, events. Finally, with this work and that of my lifelong tripmate William Lijinsky as models, it is suggested that a “non-hypothesis driven,” open-ended approach to research can be path-breaking and forefront.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 9","pages":"301-314"},"PeriodicalIF":2.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727278","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

Transcriptomic and epigenomic signatures distinguish high- and low-risk endotypes for liver tumor development 转录组和表观基因组特征可区分肝脏肿瘤发生的高风险和低风险内型。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2024-11-26 DOI: 10.1002/em.22639

Sandra L. Grimm, Tia Talley, Rahul K. Jangid, Amrit Koirala, Micah B. Castillo, Preethi H. Gunaratne, Cristian Coarfa, Cheryl L. Walker

{"title":"Transcriptomic and epigenomic signatures distinguish high- and low-risk endotypes for liver tumor development","authors":"Sandra L. Grimm, Tia Talley, Rahul K. Jangid, Amrit Koirala, Micah B. Castillo, Preethi H. Gunaratne, Cristian Coarfa, Cheryl L. Walker","doi":"10.1002/em.22639","DOIUrl":"10.1002/em.22639","url":null,"abstract":"The epigenome is a target for environmental exposures and a potential determinant of inter-individual differences in response. In genetically identical C57Bl/6 mice exposed from gestation to weaning to the endocrine-disrupting chemical (EDC) tributyltin (TBT), hepatic tumor development later in life varied across multiple cohorts over time and depending on sex and diet. In one cohort where approximately half of TBT-exposed male mice developed liver tumors at 10 months (Katz et al. Hepatic tumor formation in adult mice developmentally exposed to organotin, Environmental Health Perspectives, 128 (1), 17010, 2020), transcriptomic (RNA-seq) and epigenomic (ChIP-seq) profiling was performed on blood and liver tissue from mice that developed tumors (i.e., “high-risk”) and equivalently exposed mice did not (i.e., “low-risk”). Blood transcriptomic signatures separated TBT-exposed from vehicle controls but did not discriminate between animals that developed tumors versus those that did not. However, uninvolved liver tissue of mice with tumors exhibited transcriptomic and epigenomic signatures distinct from liver tissue of mice without tumors and had many features in common with tumors. These high-risk transcriptomic and epigenomic features were also found in 10/26 TBT-exposed mice at 5 months, indicating that this risk signature preceded tumor development. Thus, while early life exposure to TBT exhibits variable penetrance for hepatic tumor development, indicating TBT exposure is not sufficient for liver tumorigenesis, increased risk for hepatic tumor development is linked to epigenomic and transcriptomic reprogramming of the liver induced by this EDC.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 9","pages":"351-359"},"PeriodicalIF":2.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715689","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

Bruce Nathan Ames, 1928–2024: A meaningful scientific life 布鲁斯-内森-艾姆斯，1928-2024：有意义的科学人生

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2024-11-21 DOI: 10.1002/em.22641

Errol Zeiger

引用次数: 0

Investigation of mutagenicity of styrene in tumor target and non-target tissues of transgenic Big Blue® mice 苯乙烯在转基因大蓝®小鼠肿瘤靶组织和非靶组织中的诱变性调查。

IF 2.3 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2024-11-15 DOI: 10.1002/em.22638

B. Bhaskar Gollapudi, Karen Philp, Jeffrey T. Weinberg

{"title":"Investigation of mutagenicity of styrene in tumor target and non-target tissues of transgenic Big Blue® mice","authors":"B. Bhaskar Gollapudi, Karen Philp, Jeffrey T. Weinberg","doi":"10.1002/em.22638","DOIUrl":"10.1002/em.22638","url":null,"abstract":"Styrene has been shown to induce lung tumors in mice, but not in rats. The current study investigated the potential role of genotoxicity as an initial key event in the mode of action for styrene-induced lung tumors in mice. Transgenic male B6C3F1 Big Blue® mice were treated by oral gavage for 28 consecutive days with 0 (corn oil), 75, 150, or 300 mg/kg/day of styrene. The 300 mg/kg/day represented the tumorigenic dose in the oral gavage carcinogenicity study conducted in B6C3F1 mice. Following a 28-day expression period, mutant frequencies were assessed at the cII locus of the transgene in the tumor target (lung) and non-target tissues (liver, glandular stomach, and duodenum). Mice treated with N-ethyl-N-nitrosourea (40 mg/kg/day) by oral gavage on Days 1, 2, and 3 of the study and sacrificed on Day 56 served as the positive control group. Genomic DNA was extracted from the selected tissues, processed for the recovery of the transgene into infectious phage, plated onto Escherichia coli strain G1250, and incubated at 37°C for titer determination or at 24°C for the selection of mutant plaques. There were no treatment-related increases in mutant frequency in any of the tissues. The positive control group had a significant increase in the frequency of cII mutants assuring the adequacy of the experimental conditions to detect induced mutations. To conclude, mutagenicity is not considered a plausible initial key event in the mode of action for styrene-induced mouse lung tumors as these data support that styrene is not an in vivo mutagen.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"66 1-2","pages":"34-44"},"PeriodicalIF":2.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615498","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