Mutation research. Genetic toxicology and environmental mutagenesis最新文献

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Slovakian glass fibre factory genotoxicity biomonitoring study – unsupported adverse outcome pathway (AOP) from the toxicology and human epidemiological experience of synthetic vitreous fibres (SVFs) 斯洛伐克玻璃纤维厂基因毒性生物监测研究--从合成玻璃纤维(SVF)的毒理学和人类流行病学经验中得出的未获支持的不良后果途径(AOP)
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503769
Amy K. Madl, Kara Keeton
{"title":"Slovakian glass fibre factory genotoxicity biomonitoring study – unsupported adverse outcome pathway (AOP) from the toxicology and human epidemiological experience of synthetic vitreous fibres (SVFs)","authors":"Amy K. Madl,&nbsp;Kara Keeton","doi":"10.1016/j.mrgentox.2024.503769","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503769","url":null,"abstract":"<div><p>The article by Ceppi and colleagues, Genotoxic Effects of Occupational Exposure to, Glass Fibres – A Human Biomonitoring Study, published in Mutation Research –Genetic Toxicology and Environmental Mutagenesis in 2023 was reviewed with great interest. The authors undertook a novel approach to conducting a biomonitoring study of genotoxicity markers among a population of glass fibre manufacturing workers in Slovakia. On the surface, the Ceppi et al. (2023) study provides an interesting application of genotoxicity markers among a human population of workers to explore potential markers of effect (DNA strand breaks) and potential risk of susceptibility (e.g., genetic damage, disease, death). However, limited data for exposure reconstruction, uncertain influences from smoking history, and lack of consideration of decades of human epidemiology research showing no increased risk of malignant or non-malignant respiratory disease and mortality among glass fibre manufacturing workers, reveals that the conclusions of the authors are overreaching and inconsistent with the existing science. The limitations of this study preclude the ability to draw causal inferences or conclusions about DNA strand breaks as a marker of exposure, effect, or susceptibility within this population of Slovakian glass fibre workers. Further longitudinal research is required (e.g., more robust temporal assessment of occupational exposures – fibres and other compounds – and smoking history) to support the study conclusions.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503769"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072877","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
Tetraploidy as a metastable state towards malignant cell transformation within a systemic approach of cancer development 四倍体是癌症发展系统方法中恶性细胞转化的一种可转移状态
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503764
Micheline Kirsch-Volders , Miroslav Mišík , Jacques de Gerlache
{"title":"Tetraploidy as a metastable state towards malignant cell transformation within a systemic approach of cancer development","authors":"Micheline Kirsch-Volders ,&nbsp;Miroslav Mišík ,&nbsp;Jacques de Gerlache","doi":"10.1016/j.mrgentox.2024.503764","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503764","url":null,"abstract":"<div><p>Tetraploidy, a condition in which a cell has four homologous sets of chromosomes, may be a natural physiological condition or pathophysiological such as in cancer cells or stress induced tetraploidisation. Its contribution to cancer development is well known. However, among the many models proposed to explain the causes, mechanisms and steps of malignant cell transformation, only few integrate tetraploidization into a systemic multistep approach of carcinogenesis. Therefore, we will i) describe the molecular and cellular characteristics of tetraploidy; ii) assess the contribution of stress-induced tetraploidy in cancer development; iii) situate tetraploidy as a metastable state leading to cancer development in a systemic cell-centered approach; iiii) consider knowledge gaps and future perspectives. The available data shows that stress-induced tetraploidisation/polyploidisation leads to p53 stabilisation, cell cycle arrest, followed by cellular senescence or apoptosis, suppressing the proliferation of tetraploid cells. However, if tetraploid cells escape the G1-tetraploidy checkpoint, it may lead to uncontrolled proliferation of tetraploid cells, micronuclei induction, aneuploidy and deploidisation. In addition, tetraploidization favors 3D-chromatin changes and epigenetic effects. The combined effects of genetic and epigenetic changes allow the expression of oncogenic gene expression and cancer progression. Moreover, since micronuclei are inducing inflammation, which in turn may induce additional tetraploidization, tetraploidy-derived genetic instability leads to a carcinogenic vicious cycle. The concept that polyploid cells are metastable intermediates between diploidy and aneuploidy is not new. Metastability denotes an intermediate energetic state within a dynamic system other than the system’s state at least energy. Considering in parallel the genetic/epigenetic changes and the probable entropy levels induced by stress-induced tetraploidisation provides a new systemic approach to describe cancer development.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503764"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383571824000408/pdfft?md5=74e6424436801031cadd5c6455fecdde&pid=1-s2.0-S1383571824000408-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946947","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
The use of effect biomarkers in chemical mixtures risk assessment – Are they still important? 在化学混合物风险评估中使用效应生物标志物--它们仍然重要吗?
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503768
Carina Ladeira
{"title":"The use of effect biomarkers in chemical mixtures risk assessment – Are they still important?","authors":"Carina Ladeira","doi":"10.1016/j.mrgentox.2024.503768","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503768","url":null,"abstract":"<div><p>Human epidemiological studies with biomarkers of effect play an invaluable role in identifying health effects with chemical exposures and in disease prevention. Effect biomarkers that measure genetic damage are potent tools to address the carcinogenic and/or mutagenic potential of chemical exposures, increasing confidence in regulatory risk assessment decision-making processes. The micronucleus (MN) test is recognized as one of the most successful and reliable assays to assess genotoxic events, which are associated with exposures that may cause cancer. To move towards the next generation risk assessment is crucial to establish bridges between standard approaches, new approach methodologies (NAMs) and tools for increase the mechanistically-based biological plausibility in human studies, such as the adverse outcome pathways (AOPs) framework. This paper aims to highlight the still active role of MN as biomarker of effect in the evolution and applicability of new methods and approaches in human risk assessment, with the positive consequence, that the new methods provide a deeper knowledge of the mechanistically-based biology of these endpoints.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503768"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383571824000445/pdfft?md5=863d6f5213431a25d7e5a7794e3880f1&pid=1-s2.0-S1383571824000445-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141067724","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
DNA damaging effects of occupational exposure to glass fibres. Response to Madl and Keeton paper 玻璃纤维职业暴露的 DNA 损伤效应。对 Madl 和 Keeton 论文的回应
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503770
Marcello Ceppi , Bozena Smolkova , Verona Buocikova , Elise Rundén-Pran , Naouale El Yamani , Eleonora Marta Longhin , Sivakumar Murugadoss , Marta Staruchova , Magdalena Barancokova , Katarina Volkovova , Erika Halašová , Soterios Kyrtopoulos , Stefano Bonassi , Andrew Collins , Maria Dusinska
{"title":"DNA damaging effects of occupational exposure to glass fibres. Response to Madl and Keeton paper","authors":"Marcello Ceppi ,&nbsp;Bozena Smolkova ,&nbsp;Verona Buocikova ,&nbsp;Elise Rundén-Pran ,&nbsp;Naouale El Yamani ,&nbsp;Eleonora Marta Longhin ,&nbsp;Sivakumar Murugadoss ,&nbsp;Marta Staruchova ,&nbsp;Magdalena Barancokova ,&nbsp;Katarina Volkovova ,&nbsp;Erika Halašová ,&nbsp;Soterios Kyrtopoulos ,&nbsp;Stefano Bonassi ,&nbsp;Andrew Collins ,&nbsp;Maria Dusinska","doi":"10.1016/j.mrgentox.2024.503770","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503770","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503770"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090106","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
Liver-on-chip model and application in predictive genotoxicity and mutagenicity of drugs 肝芯片模型及其在预测药物遗传毒性和致突变性中的应用
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503762
B. Kopp , A. Khawam , K. Di Perna , D. Lenart , M. Vinette , R. Silva , T.B. Zanoni , C. Rore , G. Guenigault , E. Richardson , T. Kostrzewski , A. Boswell , P. Van , C. Valentine III , J. Salk , A. Hamel
{"title":"Liver-on-chip model and application in predictive genotoxicity and mutagenicity of drugs","authors":"B. Kopp ,&nbsp;A. Khawam ,&nbsp;K. Di Perna ,&nbsp;D. Lenart ,&nbsp;M. Vinette ,&nbsp;R. Silva ,&nbsp;T.B. Zanoni ,&nbsp;C. Rore ,&nbsp;G. Guenigault ,&nbsp;E. Richardson ,&nbsp;T. Kostrzewski ,&nbsp;A. Boswell ,&nbsp;P. Van ,&nbsp;C. Valentine III ,&nbsp;J. Salk ,&nbsp;A. Hamel","doi":"10.1016/j.mrgentox.2024.503762","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503762","url":null,"abstract":"<div><p>Currently, there is no test system, whether <em>in vitro</em> or <em>in vivo</em>, capable of examining all endpoints required for genotoxicity evaluation used in pre-clinical drug safety assessment. The objective of this study was to develop a model which could assess all the required endpoints and possesses robust human metabolic activity, that could be used in a streamlined, animal-free manner. Liver-on-chip (LOC) models have intrinsic human metabolic activity that mimics the in vivo environment, making it a preferred test system. For our assay, the LOC was assembled using primary human hepatocytes or HepaRG cells, in a MPS-T12 plate, maintained under microfluidic flow conditions using the PhysioMimix® Microphysiological System (MPS), and co-cultured with human lymphoblastoid (TK6) cells in transwells. This system allows for interaction between two compartments and for the analysis of three different genotoxic endpoints, i.e. DNA strand breaks (comet assay) in hepatocytes, chromosome loss or damage (micronucleus assay) and mutation (Duplex Sequencing) in TK6 cells. Both compartments were treated at 0, 24 and 45 h with two direct genotoxicants: methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), and two genotoxicants requiring metabolic activation: benzo[<em>a</em>]pyrene (B[<em>a</em>]P) and cyclophosphamide (CP). Assessment of cytochrome activity, RNA expression, albumin, urea and lactate dehydrogenase production, demonstrated functional metabolic capacities. Genotoxicity responses were observed for all endpoints with MMS and EMS. Increases in the micronucleus and mutations (MF) frequencies were also observed with CP, and %Tail DNA with B[<em>a</em>]P, indicating the metabolic competency of the test system. CP did not exhibit an increase in the %Tail DNA, which is in line with <em>in vivo</em> data. However, B[<em>a</em>]P did not exhibit an increase in the % micronucleus and MF, which might require an optimization of the test system. In conclusion, this proof-of-principle experiment suggests that LOC-MPS technology is a promising tool for <em>in vitro</em> hazard identification genotoxicants.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503762"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825246","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
Dapagliflozin suppresses diabetes-induced oxidative DNA damage and hypermethylation in mouse somatic cells 达帕格列净可抑制糖尿病诱导的小鼠体细胞氧化 DNA 损伤和高甲基化
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503765
Sabry M. Attia , Norah A. Albekairi , Ali A. Alshamrani , Sheikh F. Ahmad , Faris Almutairi , Mohamed S.M. Attia , Mushtaq A. Ansari , Saleh A. Bakheet , Gamaleldin I. Harisa , Ahmed Nadeem
{"title":"Dapagliflozin suppresses diabetes-induced oxidative DNA damage and hypermethylation in mouse somatic cells","authors":"Sabry M. Attia ,&nbsp;Norah A. Albekairi ,&nbsp;Ali A. Alshamrani ,&nbsp;Sheikh F. Ahmad ,&nbsp;Faris Almutairi ,&nbsp;Mohamed S.M. Attia ,&nbsp;Mushtaq A. Ansari ,&nbsp;Saleh A. Bakheet ,&nbsp;Gamaleldin I. Harisa ,&nbsp;Ahmed Nadeem","doi":"10.1016/j.mrgentox.2024.503765","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503765","url":null,"abstract":"<div><p>Diabetes mellitus is a complex metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors that increase the risk of cancer development. However, it is unclear whether the increased cancer risk is due to poor glycemic control or the use of some antidiabetic medications. Therefore, we investigated the genetic and epigenetic changes in somatic cells in a mouse model of diabetes and studied whether multiple exposures to the antidiabetic medication dapagliflozin influence these changes. We also elucidated the mechanism(s) of these ameliorations. The micronucleus test and modified comet assay were used to investigate bone marrow DNA damage and methylation changes. These assays revealed that dapagliflozin is non-genotoxic in the tested regimen, and oxidative DNA damage and hypermethylation were significantly higher in diabetic mice. Spectrophotometry also evaluated oxidative DNA damage and global DNA methylation, revealing similar significant alterations induced by diabetes. Conversely, the dapagliflozin-treated diabetic animals significantly reduced these changes. The expression of some genes involved in DNA repair and DNA methylation was disrupted considerably in the somatic cells of diabetic animals. In contrast, dapagliflozin treatment significantly restored these disruptions and enhanced DNA repair. The simultaneous effects of decreased oxidative DNA damage and hypermethylation levels suggest that dapagliflozin can be used as a safe antidiabetic drug to reduce DNA damage and hypermethylation in diabetes, demonstrating its usefulness in patients with diabetes to control hyperglycemia and decrease the development of its subsequent complications.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503765"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140918240","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
Genotoxicity assessments of N-nitrosoethylisopropylamine (NEIPA) and N-nitrosodiisopropylamine (NDIPA) in the C57BL/6J mouse 在 C57BL/6J 小鼠体内评估 N-亚硝基乙基异丙基胺(NEIPA)和 N-亚硝基二异丙基胺(NDIPA)的遗传毒性
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503763
Qian Ye , Xingchao Geng , Hua Jiang , Chao Qin , Hui Wu , Sanlong Wang , Hairuo Wen
{"title":"Genotoxicity assessments of N-nitrosoethylisopropylamine (NEIPA) and N-nitrosodiisopropylamine (NDIPA) in the C57BL/6J mouse","authors":"Qian Ye ,&nbsp;Xingchao Geng ,&nbsp;Hua Jiang ,&nbsp;Chao Qin ,&nbsp;Hui Wu ,&nbsp;Sanlong Wang ,&nbsp;Hairuo Wen","doi":"10.1016/j.mrgentox.2024.503763","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503763","url":null,"abstract":"<div><p>N-Nitrosamines, known as drug impurities and suspected carcinogens, have drawn significant public concern. In response to drug regulatory needs, the European Medicines Agency (EMA) has previously proposed a carcinogenic potency categorization approach based on the N-nitrosamine α-hydroxylation hypothesis, i.e., that N-nitrosamine mutagenicity increases with the number of α-hydrogen atoms. However, this structure-activity relationship has not been fully tested <em>in vivo</em>. NEIPA (N-nitrosoethylisopropylamine) and NDIPA (N-nitrosodiisopropylamine) are small N-Nitrosamines with similar structures, differing in that the former compound has an additional α-hydrogen atom. In this study, NEIPA and NEIPA doses, 25–100 mg/kg, were administered orally to C57BL/6 J mice for seven consecutive days, and their mutation and DNA damage effects were compared. Compared with NDIPA, the mutagenicity and DNA damage potencies of NEIPA (which contains one more α-hydrogen) were much greater. These differences may be related to their distinct metabolic pathways and target organs. This case study confirms the role of α-hydroxyl modification in the mutagenicity of nitrosamines, with oxidation at the α-hydrogen being a crucial step in the formation of mutagens from N-Nitrosamines, and can inform mutagenicity risk assessment and the formulation of regulatory standards for N-nitrosamine impurities.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503763"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878583","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
Human plasma can modulate micronucleus frequency in TK6 and OE33 cells in vitro 人血浆可调节体外 TK6 和 OE33 细胞的微核频率
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-05-01 DOI: 10.1016/j.mrgentox.2024.503766
Hamsa Naser , Kathryn Munn , Rachel Lawrence , Rhiannon Wright , Ethan Grewal , Lisa Williams , Shareen Doak , Gareth Jenkins
{"title":"Human plasma can modulate micronucleus frequency in TK6 and OE33 cells in vitro","authors":"Hamsa Naser ,&nbsp;Kathryn Munn ,&nbsp;Rachel Lawrence ,&nbsp;Rhiannon Wright ,&nbsp;Ethan Grewal ,&nbsp;Lisa Williams ,&nbsp;Shareen Doak ,&nbsp;Gareth Jenkins","doi":"10.1016/j.mrgentox.2024.503766","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503766","url":null,"abstract":"<div><p>In this paper, we studied the potential genotoxic effects of human plasma from healthy volunteers, as well as patients with gastro-oesophageal reflux disease, Barrett’s oesophagus (BO) and oesophageal adenocarcinoma (OAC) using the oesophageal adenocarcinoma cell line (OE33) and the lymphoblastoid cell line (TK6). Both TK6 and OE33 cells were treated with plasma (10 % volume, replacing foetal bovine serum (FBS) or horse serum (HS)) at different time points of 4 h (for the micronucleus (Mn) assay and the invasion assay) and 24 h (for the cell cycle studies). Plasma-induced effects on DNA damage levels, cell viability and the cell cycle were studied by the micronucleus assay, cytokinesis block proliferation index (CBPI) and flow cytometry respectively. The expression of IL-8 in supernatants of TK6 cells and IFN-β in OE33 cells was also analysed by enzyme-linked immunosorbent assay (ELISA). Finally, we carried out an assessment of cellular invasion of OE33 cells following plasma treatment.</p><p>The results of the micronucleus assay confirmed the genotoxicity of direct plasma treatment from some participants through the increase in DNA damage in TK6 cells. Conversely, some individual patient plasma samples reduced background levels of TK6 cell Mn frequency, in an anti-genotoxic fashion. In TK6 cells, (on average) plasma samples from patients with Barrett’s oesophagus induced higher micronucleus levels than healthy volunteers (p= 0.0019). There was little difference in Mn induction when using plasma versus serum to treat the cells <em>in vitro</em>. Cell cycle results showed that direct plasma treatment had a marked impact on OE33 cells at 24 h (p=0.0182 for BO and p=0.0320 for OAC) by decreasing the proportion of cells in the S phase, while plasma exposure was less impactful on the cell cycle of TK6 cells. Invasion of OE33 cells was also seen to be non-significantly affected by plasma treatment of OE33 cells.</p><p>The addition of N-acetyl cysteine NAC in a dose-dependent matter did not alter the formation of Mn in TK6 cells, suggesting that reactive oxygen species (ROS) are not the root cause of plasma’s genotoxicity. The concentration of IL-8 in TK6 cells and IFN-β in OE33 cells was significantly higher in cells treated with OAC-derived plasma than in the untreated negative control. Collectively, our results demonstrate that plasma-specific effects are detectable which helps us better understand some important aspects of the biology of blood-based biomarkers under development.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503766"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383571824000421/pdfft?md5=3e31a9910a81e163045bcfff14c96be0&pid=1-s2.0-S1383571824000421-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077904","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
Recent advances in high-performance liquid chromatography tandem mass spectrometry techniques for analysis of DNA damage and epigenetic modifications 用于分析 DNA 损伤和表观遗传修饰的高效液相色谱串联质谱技术的最新进展
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-03-30 DOI: 10.1016/j.mrgentox.2024.503755
Shaokun Chen , Weiyi Lai , Hailin Wang
{"title":"Recent advances in high-performance liquid chromatography tandem mass spectrometry techniques for analysis of DNA damage and epigenetic modifications","authors":"Shaokun Chen ,&nbsp;Weiyi Lai ,&nbsp;Hailin Wang","doi":"10.1016/j.mrgentox.2024.503755","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503755","url":null,"abstract":"<div><p>Environmental exposure would cause DNA damage and epigenetic modification changes, potentially resulting in physiological dysfunction, thereby triggering diseases and even cancer. DNA damage and epigenetic modifications are thus promising biomarkers for environmental exposures and disease states. Benefiting from its high sensitivity and accuracy, high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is considered the “gold standard technique” for investigating epigenetic DNA modifications. This review summarizes the recent advancements of UHPLC-MS/MS-based technologies for DNA damage and epigenetic modifications analysis, mainly focusing on the innovative methods developed for UHPLC-MS/MS-related pretreatment technologies containing efficient genomic DNA digestion and effective removal of the inorganic salt matrix, and the new strategies for improving detection sensitivity of liquid chromatography-mass spectrometry. Moreover, we also summarized the novel hyphenated techniques of the advanced UHPLC-MS/MS coupled with other separation and analysis methods for the measurement of DNA damage and epigenetic modification changes in special regions and fragments of chromosomes.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503755"},"PeriodicalIF":1.9,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140339165","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
Micronuclei and other nuclear anomalies in exfoliated urothelial cells and urinary 8-hydroxy-deoxyguanosine levels among Turkish hairdressers 土耳其理发师脱落尿道细胞中的微核和其他核异常以及尿液中的 8-羟基脱氧鸟苷水平
IF 1.9 4区 医学
Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-03-29 DOI: 10.1016/j.mrgentox.2024.503754
Ayca Aktas Sukuroglu , Sema Burgaz
{"title":"Micronuclei and other nuclear anomalies in exfoliated urothelial cells and urinary 8-hydroxy-deoxyguanosine levels among Turkish hairdressers","authors":"Ayca Aktas Sukuroglu ,&nbsp;Sema Burgaz","doi":"10.1016/j.mrgentox.2024.503754","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2024.503754","url":null,"abstract":"<div><p>Hairdressers are constantly occupationally exposed to many chemicals have the potential to cause allergies and carcinogenic effects, act as skin and eye irritants and induce oxidative stress and DNA damage. This study aimed to evaluate occupation-induced genotoxicity based on the presence of micronucleus (MN) and other nuclear anomalies in urothelial cells and measure oxidative DNA damage based on the 8-hydroxy-2’-deoxyguanosine level in the urine of Turkish hairdressers. Originality of this study comes from that there was no study on MN and other nuclear anomalies frequencies and oxidative DNA damage in urine samples of hairdressers in the literature. The mean±standard deviation frequency (‰) of micronucleated (MNed) cells was higher in the hairdresser group (n=56) (4.81±7.87, <em>p</em>&lt;0.001) than in the control group (n=56) (0.93±1.85). Nuclear buds were not observed in either group. While the frequency of basal cells was higher in the control group (446.6±106.21) than in the hairdresser group (367.78±101.51, <em>p</em>&lt;0.001), the frequency of binuclear, karyolytic, pycnotic and karyorrhectic cells were higher in the hairdresser group (0.41±0.80, <em>p</em>&lt;0.001; 438.02±118.27, <em>p</em>&lt;0.001; 0.43±0.76, <em>p</em>&lt;0.001; and 47.27±28.40, <em>p</em>&lt;0.001) than in the control group (0.04±0.27, 358.57±95.71, 0.05±0.23 and 24.41±14.50). Condensed chromatins were observed only in the hairdresser group. Specific gravity adjusted 8-hydroxy-2’-deoxyguanosine level was statistically lower in the hairdresser group (908.21±403.25 ng/mL-SG) compared to the control group (1003.09±327.09 ng/mL-SG) (<em>p</em>=0.024). No significant correlation was found between the 8-hydroxy-2’-deoxyguanosine level and the frequency MN. The amount of formaldehyde released during Brazilian keratin treatment was higher than the American Conference of Governmental Industrial Hygienists -Threshold Limit Value (ACGIH-TLV; 0.1 ppm). Similarly, the amount of ethyl acetate released in three salons was above the recommended limit (400 ppm). These findings suggest that hairdressers have an increased risk of genotoxicity and cytotoxicity owing to occupational exposure, regardless of age, working hours, smoking and alcohol consumption.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"896 ","pages":"Article 503754"},"PeriodicalIF":1.9,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338779","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}
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