Mutagenesis最新文献

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Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review. 长还是短?端粒长度与胰腺癌及其前体病变的关系。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-11-17 DOI: 10.1093/mutage/gead034
Daniele Campa, Alessio Felici, Chiara Corradi, Giulia Peduzzi, Manuel Gentiluomo, Riccardo Farinella, Cosmeri Rizzato
{"title":"Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review.","authors":"Daniele Campa, Alessio Felici, Chiara Corradi, Giulia Peduzzi, Manuel Gentiluomo, Riccardo Farinella, Cosmeri Rizzato","doi":"10.1093/mutage/gead034","DOIUrl":"https://doi.org/10.1093/mutage/gead034","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, with a survival approaching only 11% at five years after diagnosis. In the last 15 years, telomere length measured in leukocyte (LTL) has been studied in relation to PDAC risk. The majority of the studies reported an association between short LTL and increased PDAC risk, but the results are heterogeneous. Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) in the telomerase reverse transcriptase (TERT) gene as susceptibility loci for PDAC. Polygenic risk scores (PRS) computed using SNPs associated with LTL have been tested in relation to PDAC susceptibility with various methods and giving contrasting results. The aim of this review is to analyze all publications carried out specifically on LTL, considering LTL measured with qPCR and with genetic proxies, and PDAC risk. Additionally, we will give an overview of the most relevant associations between SNPs in telomere associated genes and PDAC, to answer the question shorter or longer? Which one of the two is associated with PDAC risk?</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398280","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
Abstracts of the 45th Annual Meeting of the United Kingdom Environmental Mutagen Society, 2nd – 5th July 2023 at Clontarf Castle Hotel, Dublin, Ireland 第45届英国环境诱变剂协会年会,2023年7月2日至5日在爱尔兰都柏林的Clontarf城堡酒店举行
4区 医学
Mutagenesis Pub Date : 2023-11-14 DOI: 10.1093/mutage/gead024
{"title":"Abstracts of the 45th Annual Meeting of the United Kingdom Environmental Mutagen Society, 2nd – 5th July 2023 at Clontarf Castle Hotel, Dublin, Ireland","authors":"","doi":"10.1093/mutage/gead024","DOIUrl":"https://doi.org/10.1093/mutage/gead024","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"114 15","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134957330","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
Visual comet scoring revisited: a guide to scoring comet assay slides and obtaining reliable results. 再次访问视觉彗星评分:彗星分析幻灯片评分和获得可靠结果的指南。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-10-14 DOI: 10.1093/mutage/gead015
Peter Møller, Amaya Azqueta, Julen Sanz-Serrano, Tamara Bakuradze, Elke Richling, Ezgi Eyluel Bankoglu, Helga Stopper, Victoria Claudino Bastos, Sabine A S Langie, Annie Jensen, Francesca Scavone, Lisa Giovannelli, Maria Wojewódzka, Marcin Kruszewski, Vanessa Valdiglesias, Blanca Laffon, Carla Costa, Solange Costa, João Paulo Teixeira, Mirko Marino, Cristian Del Bo, Patrizia Riso, Congying Zheng, Sergey Shaposhnikov, Andrew Collins
{"title":"Visual comet scoring revisited: a guide to scoring comet assay slides and obtaining reliable results.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Julen Sanz-Serrano,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo,&nbsp;Patrizia Riso,&nbsp;Congying Zheng,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead015","DOIUrl":"10.1093/mutage/gead015","url":null,"abstract":"<p><p>Measurement of DNA migration in the comet assay can be done by image analysis or visual scoring. The latter accounts for 20%-25% of the published comet assay results. Here we assess the intra- and inter-investigator variability in visual scoring of comets. We include three training sets of comet images, which can be used as reference for researchers who wish to use visual scoring of comets. Investigators in 11 different laboratories scored the comet images using a five-class scoring system. There is inter-investigator variation in the three training sets of comets (i.e. coefficient of variation (CV) = 9.7%, 19.8%, and 15.2% in training sets I-III, respectively). However, there is also a positive correlation of inter-investigator scoring in the three training sets (r = 0.60). Overall, 36% of the variation is attributed to inter-investigator variation and 64% stems from intra-investigator variation in scoring between comets (i.e. the comets in training sets I-III look slightly different and this gives rise to heterogeneity in scoring). Intra-investigator variation in scoring was also assessed by repeated analysis of the training sets by the same investigator. There was larger variation when the training sets were scored over a period of six months (CV = 5.9%-9.6%) as compared to 1 week (CV = 1.3%-6.1%). A subsequent study revealed a high inter-investigator variation when premade slides, prepared in a central laboratory, were stained and scored by investigators in different laboratories (CV = 105% and 18%-20% in premade slides with comets from unexposed and hydrogen peroxide-exposed cells, respectively). The results indicate that further standardization of visual scoring is desirable. Nevertheless, the analysis demonstrates that visual scoring is a reliable way of analysing DNA migration in comets.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"253-263"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876699","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: 3
Long-term cryopreservation of potassium bromate positive assay controls for measurement of oxidatively damaged DNA by the Fpg-modified comet assay: results from the hCOMET ring trial. 溴酸钾阳性测定对照的长期冷冻保存,通过Fpg修饰的彗星测定法测量氧化损伤的DNA:来自hCOMET环试验的结果。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-10-14 DOI: 10.1093/mutage/gead020
Peter Møller, Amaya Azqueta, Adriana Rodriguez-Garraus, Tamara Bakuradze, Elke Richling, Ezgi Eyluel Bankoglu, Helga Stopper, Victoria Claudino Bastos, Sabine A S Langie, Annie Jensen, Sara Ristori, Francesca Scavone, Lisa Giovannelli, Maria Wojewódzka, Marcin Kruszewski, Vanessa Valdiglesias, Blanca Laffon, Carla Costa, Solange Costa, João Paulo Teixeira, Mirko Marino, Cristian Del Bo', Patrizia Riso, Congying Zheng, Sergey Shaposhnikov, Andrew Collins
{"title":"Long-term cryopreservation of potassium bromate positive assay controls for measurement of oxidatively damaged DNA by the Fpg-modified comet assay: results from the hCOMET ring trial.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Adriana Rodriguez-Garraus,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Sara Ristori,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo',&nbsp;Patrizia Riso,&nbsp;Congying Zheng,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead020","DOIUrl":"10.1093/mutage/gead020","url":null,"abstract":"<p><p>The formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay is widely used for the measurement of oxidatively generated damage to DNA. However, there has not been a recommended long-term positive control for this version of the comet assay. We have investigated potassium bromate as a positive control for the Fpg-modified comet assay because it generates many Fpg-sensitive sites with a little concurrent generation of DNA strand breaks. Eight laboratories used the same procedure for the treatment of monocytic THP-1 cells with potassium bromate (0, 0.5, 1.5, and 4.5 mM) and subsequent cryopreservation in a freezing medium consisting of 50% foetal bovine serum, 40% RPMI-1640 medium, and 10% dimethyl sulphoxide. The samples were analysed by the Fpg-modified comet assay three times over a 3-year period. All laboratories obtained a positive concentration-response relationship in cryopreserved samples (linear regression coefficients ranging from 0.79 to 0.99). However, there was a wide difference in the levels of Fpg-sensitive sites between the laboratory with the lowest (4.2% Tail DNA) and highest (74% Tail DNA) values in THP-1 cells after exposure to 4.5 mM KBrO3. In an attempt to assess sources of inter-laboratory variation in Fpg-sensitive sites, comet images from one experiment in each laboratory were forwarded to a central laboratory for visual scoring. There was high consistency between measurements of %Tail DNA values in each laboratory and the visual score of the same comets done in the central laboratory (r = 0.98, P < 0.001, linear regression). In conclusion, the results show that potassium bromate is a suitable positive comet assay control.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"264-272"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042290","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: 2
Inter-laboratory variation in measurement of DNA damage by the alkaline comet assay in the hCOMET ring trial. hCOMET环试验中碱性彗星法测定DNA损伤的实验室间变异。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-10-14 DOI: 10.1093/mutage/gead014
Peter Møller, Amaya Azqueta, Miguel Collia, Tamara Bakuradze, Elke Richling, Ezgi Eyluel Bankoglu, Helga Stopper, Victoria Claudino Bastos, Sabine A S Langie, Annie Jensen, Sara Ristori, Francesca Scavone, Lisa Giovannelli, Maria Wojewódzka, Marcin Kruszewski, Vanessa Valdiglesias, Blanca Laffon, Carla Costa, Solange Costa, João Paulo Teixeira, Mirko Marino, Cristian Del Bo, Patrizia Riso, Congying Zheng, Sergey Shaposhnikov, Andrew Collins
{"title":"Inter-laboratory variation in measurement of DNA damage by the alkaline comet assay in the hCOMET ring trial.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Miguel Collia,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Sara Ristori,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo,&nbsp;Patrizia Riso,&nbsp;Congying Zheng,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead014","DOIUrl":"10.1093/mutage/gead014","url":null,"abstract":"<p><p>The comet assay is a simple and versatile method for measurement of DNA damage in eukaryotic cells. More specifically, the assay detects DNA migration from agarose gel-embedded nucleoids, which depends on assay conditions and the level of DNA damage. Certain steps in the comet assay procedure have substantial impact on the magnitude of DNA migration (e.g. electric potential and time of electrophoresis). Inter-laboratory variation in DNA migration levels occurs because there is no agreement on optimal assay conditions or suitable assay controls. The purpose of the hCOMET ring trial was to test potassium bromate (KBrO3) as a positive control for the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay. To this end, participating laboratories used semi-standardized protocols for cell culture (i.e. cell culture, KBrO3 exposure, and cryopreservation of cells) and comet assay procedures, whereas the data acquisition was not standardized (i.e. staining of comets and image analysis). Segregation of the total variation into partial standard deviation (SD) in % Tail DNA units indicates the importance of cell culture procedures (SD = 10.9), comet assay procedures (SD = 12.3), staining (SD = 7.9) and image analysis (SD = 0.5) on the overall inter-laboratory variation of DNA migration (SD = 18.2). Future studies should assess sources of variation in each of these steps. On the positive side, the hCOMET ring trial demonstrates that KBrO3 is a robust positive control for the Fpg-modified comet assay. In conclusion, the hCOMET ring trial has demonstrated a high reproducibility of detecting genotoxic effects by the comet assay, but inter-laboratory variation of DNA migration levels is a concern.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"283-294"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876152","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: 4
DNA strand break levels in cryopreserved mononuclear blood cell lines measured by the alkaline comet assay: results from the hCOMET ring trial. 通过碱性彗星试验测量的冷冻保存的单核血细胞系中的DNA链断裂水平:来自hCOMET环试验的结果。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-10-14 DOI: 10.1093/mutage/gead019
Peter Møller, Amaya Azqueta, Adriana Rodriguez-Garraus, Tamara Bakuradze, Elke Richling, Ezgi Eyluel Bankoglu, Helga Stopper, Victoria Claudino Bastos, Sabine A S Langie, Annie Jensen, Sara Ristori, Francesca Scavone, Lisa Giovannelli, Maria Wojewódzka, Marcin Kruszewski, Vanessa Valdiglesias, Blanca Laffon, Carla Costa, Solange Costa, João Paulo Teixeira, Mirko Marino, Cristian Del Bo', Patrizia Riso, Congying Zhang, Sergey Shaposhnikov, Andrew Collins
{"title":"DNA strand break levels in cryopreserved mononuclear blood cell lines measured by the alkaline comet assay: results from the hCOMET ring trial.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Adriana Rodriguez-Garraus,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Sara Ristori,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo',&nbsp;Patrizia Riso,&nbsp;Congying Zhang,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead019","DOIUrl":"10.1093/mutage/gead019","url":null,"abstract":"<p><p>The comet assay is widely used in biomonitoring studies for the analysis of DNA damage in leukocytes and peripheral blood mononuclear cells. Rather than processing blood samples directly, it can be desirable to cryopreserve whole blood or isolated cells for later analysis by the comet assay. However, this creates concern about artificial accumulation of DNA damage during cryopreservation. In this study, 10 laboratories used standardized cryopreservation and thawing procedures of monocytic (THP-1) or lymphocytic (TK6) cells. Samples were cryopreserved in small aliquots in 50% foetal bovine serum, 40% cell culture medium, and 10% dimethyl sulphoxide. Subsequently, cryopreserved samples were analysed by the standard comet assay on three occasions over a 3-year period. Levels of DNA strand breaks in THP-1 cells were increased (four laboratories), unaltered (four laboratories), or decreased (two laboratories) by long-term storage. Pooled analysis indicates only a modest positive association between storage time and levels of DNA strand breaks in THP-1 cells (0.37% Tail DNA per year, 95% confidence interval: -0.05, 0.78). In contrast, DNA strand break levels were not increased by cryopreservation in TK6 cells. There was inter-laboratory variation in levels of DNA strand breaks in THP-1 cells (SD = 3.7% Tail DNA) and TK6 reference sample cells (SD = 9.4% Tail DNA), whereas the intra-laboratory residual variation was substantially smaller (i.e. SD = 0.4%-2.2% Tail DNA in laboratories with the smallest and largest variation). In conclusion, the study shows that accumulation of DNA strand breaks in cryopreserved mononuclear blood cell lines is not a matter of concern.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"273-282"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060071","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: 1
Obituary to John Ashby (19 April 1943-03 October 2022). 约翰·阿什比的讣告(1940年4月19日至2022年10月3日)。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-10-14 DOI: 10.1093/mutage/gead026
David Kirkland, George Douglas
{"title":"Obituary to John Ashby (19 April 1943-03 October 2022).","authors":"David Kirkland,&nbsp;George Douglas","doi":"10.1093/mutage/gead026","DOIUrl":"10.1093/mutage/gead026","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"251-252"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10388184","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
Next Generation Sequencing Workshop at the Royal Society of Medicine (London, May 2022): how genomics is on the path to modernizing genetic toxicology. 英国皇家医学会下一代测序研讨会(伦敦,2022年5月):基因组学如何走上基因毒理学现代化的道路。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-08-24 DOI: 10.1093/mutage/gead012
Anthony M Lynch, Thalita B Zanoni, Jesse J Salk, Inigo Martincorena, Robert R Young, Jill Kucab, Charles C Valentine, Carole Yauk, Patricia A Escobar, Kristine L Witt, Roland Frötschl, Simon H Reed, Anne Ashford
{"title":"Next Generation Sequencing Workshop at the Royal Society of Medicine (London, May 2022): how genomics is on the path to modernizing genetic toxicology.","authors":"Anthony M Lynch, Thalita B Zanoni, Jesse J Salk, Inigo Martincorena, Robert R Young, Jill Kucab, Charles C Valentine, Carole Yauk, Patricia A Escobar, Kristine L Witt, Roland Frötschl, Simon H Reed, Anne Ashford","doi":"10.1093/mutage/gead012","DOIUrl":"10.1093/mutage/gead012","url":null,"abstract":"<p><p>The use of error-corrected Next Generation Sequencing (ecNG) to determine mutagenicity has been a subject of growing interest and potentially a disruptive technology that could supplement, and in time, replace current testing paradigms in preclinical safety assessment. Considering this, a Next Generation Sequencing Workshop was held at the Royal Society of Medicine in London in May 2022, supported by the United Kingdom Environmental Mutagen Society (UKEMS) and TwinStrand Biosciences (WA, USA), to discuss progress and future applications of this technology. In this meeting report, the invited speakers provide an overview of the Workshop topics covered and identify future directions for research. In the area of somatic mutagenesis, several speakers reviewed recent progress made with correlating ecNGS to classic in vivo transgenic rodent mutation assays as well as exploring the use of this technology directly in humans and animals, and in complex organoid models. Additionally, ecNGS has been used for detecting off-target effects of gene editing tools and emerging data suggest ecNGS potential to measure clonal expansion of cells carrying mutations in cancer driver genes as an early marker of carcinogenic potential and for direct human biomonitoring. As such, the workshop demonstrated the importance of raising awareness and support for advancing the science of ecNGS for mutagenesis, gene editing, and carcinogenesis research. Furthermore, the potential of this new technology to contribute to advances in drug and product development and improve safety assessment was extensively explored.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"192-200"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439776","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
Genotoxicity of cytokines at chemotherapy-induced 'storm' concentrations in a model of the human bone marrow. 在人类骨髓模型中化疗诱导的“风暴”浓度下细胞因子的遗传毒性。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-08-24 DOI: 10.1093/mutage/gead018
Harshini S H Asurappulige, Adam D Thomas, H Ruth Morse
{"title":"Genotoxicity of cytokines at chemotherapy-induced 'storm' concentrations in a model of the human bone marrow.","authors":"Harshini S H Asurappulige,&nbsp;Adam D Thomas,&nbsp;H Ruth Morse","doi":"10.1093/mutage/gead018","DOIUrl":"10.1093/mutage/gead018","url":null,"abstract":"<p><p>Donor cell leukaemia (DCL) is a complication of haematopoietic stem cell transplantation where donated cells become malignant within the patient's bone marrow. As DCL predominates as acute myeloid leukaemia, we hypothesized that the cytokine storm following chemotherapy played a role in promoting and supporting leukaemogenesis. Cytokines have also been implicated in genotoxicity; thus, we explored a cell line model of the human bone marrow (BM) to secrete myeloid cytokines following drug treatment and their potential to induce micronuclei. HS-5 human stromal cells were exposed to mitoxantrone (MTX) and chlorambucil (CHL) and, for the first time, were profiled for 80 cytokines using an array. Fifty-four cytokines were detected in untreated cells, of which 24 were upregulated and 10 were downregulated by both drugs. FGF-7 was the lowest cytokine to be detected in both untreated and treated cells. Eleven cytokines not detected at baseline were detected following drug exposure. TNFα, IL6, GM-CSF, G-CSF, and TGFβ1 were selected for micronuclei induction. TK6 cells were exposed to these cytokines in isolation and in paired combinations. Only TNFα and TGFβ1 induced micronuclei at healthy concentrations, but all five cytokines induced micronuclei at storm levels, which was further increased when combined in pairs. Of particular concern was that some combinations induced micronuclei at levels above the mitomycin C positive control; however, most combinations were less than the sum of micronuclei induced following exposure to each cytokine in isolation. These data infer a possible role for cytokines through chemotherapy-induced cytokine storm, in the instigation and support of leukaemogenesis in the BM, and implicate the need to evaluate individuals for variability in cytokine secretion as a potential risk factor for complications such as DCL.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"201-215"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/09/gead018.PMC10448863.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074044","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
Impact of mobile phone-specific electromagnetic fields on DNA damage caused by occupationally relevant exposures: results of ex vivo experiments with peripheral blood mononuclear cells from different demographic groups. 手机特定电磁场对职业相关暴露引起的DNA损伤的影响:不同人群外周血单核细胞的离体实验结果。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-08-24 DOI: 10.1093/mutage/gead022
Miroslav Mišík, Michael Kundi, Nadine Worel, Franziska Ferk, Hans-Peter Hutter, Michael Grusch, Armen Nersesyan, Denise Herrera Morales, Siegfried Knasmueller
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