Mutagenesis最新文献

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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
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 2.5 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":2.5,"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
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
{"title":"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.","authors":"Miroslav Mišík,&nbsp;Michael Kundi,&nbsp;Nadine Worel,&nbsp;Franziska Ferk,&nbsp;Hans-Peter Hutter,&nbsp;Michael Grusch,&nbsp;Armen Nersesyan,&nbsp;Denise Herrera Morales,&nbsp;Siegfried Knasmueller","doi":"10.1093/mutage/gead022","DOIUrl":"10.1093/mutage/gead022","url":null,"abstract":"<p><p>The aim of this study was to investigate if age and body mass of humans have an impact on the DNA-damaging properties of high-frequency mobile phone-specific electromagnetic fields (HF-EMF, 1950 MHz, universal mobile telecommunications system, UMTS signal) and if this form of radiation has an impact on the genotoxic effects of occupationally relevant exposures. Pooled peripheral blood mononuclear cells (PBMC) from three groups [young normal weight, young obese (YO), and older age normal weight individuals] were exposed to different doses of HF-EMF (0.25, 0.5, and 1.0 W/kg specific absorption rate-SAR) and simultaneously or sequentially to different chemicals which cause DNA damage (CrO3, NiCl2, benzo[a]pyrene diol epoxide-BPDE, and 4-nitroquinoline 1-oxide-4NQO) via different molecular mechanisms. We found no difference in regard to the background values in the three groups but a significant increase of DNA damage (81% without and 36% with serum) in cells from old participants after radiation with 1.0 W/kg SAR 16 h. In combined treatment experiments we found no impact of the UMTS signal on chemically induced DNA damage in the different groups in general. However, a moderate decrease of DNA damage was seen in simultaneous treatment experiments with BPDE and 1.0 W/kg SAR in the YO group (decline 18%). Taken together our findings indicate that HF-EMF cause DNA damage in PBMC from older subjects (69.1 years). Furthermore, they show that the radiation does not increase induction of DNA damage by occupationally relevant chemicals.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"227-237"},"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/23/b5/gead022.PMC10448860.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10072483","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 by rapeseed methyl ester and hydrogenated vegetable oil combustion exhaust products in lung epithelial (A549) cells. 油菜籽甲酯和氢化植物油燃烧废气在肺上皮(A549)细胞中的遗传毒性。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-08-24 DOI: 10.1093/mutage/gead016
Monika Hezareh Rothmann, Peter Møller, Yona J Essig, Louise Gren, Vilhelm B Malmborg, Martin Tunér, Joakim Pagels, Annette M Krais, Martin Roursgaard
{"title":"Genotoxicity by rapeseed methyl ester and hydrogenated vegetable oil combustion exhaust products in lung epithelial (A549) cells.","authors":"Monika Hezareh Rothmann,&nbsp;Peter Møller,&nbsp;Yona J Essig,&nbsp;Louise Gren,&nbsp;Vilhelm B Malmborg,&nbsp;Martin Tunér,&nbsp;Joakim Pagels,&nbsp;Annette M Krais,&nbsp;Martin Roursgaard","doi":"10.1093/mutage/gead016","DOIUrl":"10.1093/mutage/gead016","url":null,"abstract":"<p><p>Biofuel is an attractive substitute for petrodiesel because of its lower environmental footprint. For instance, the polycyclic aromatic hydrocarbons (PAH) emission per fuel energy content is lower for rapeseed methyl ester (RME) than for petrodiesel. This study assesses genotoxicity by extractable organic matter (EOM) of exhaust particles from the combustion of petrodiesel, RME, and hydrogenated vegetable oil (HVO) in lung epithelial (A549) cells. Genotoxicity was assessed as DNA strand breaks by the alkaline comet assay. EOM from the combustion of petrodiesel and RME generated the same level of DNA strand breaks based on the equal concentration of total PAH (i.e. net increases of 0.13 [95% confidence interval (CI): 0.002, 0.25, and 0.12 [95% CI: 0.01, 0.24] lesions per million base pairs, respectively). In comparison, the positive control (etoposide) generated a much higher level of DNA strand breaks (i.e. 0.84, 95% CI: 0.72, 0.97) lesions per million base pairs. Relatively low concentrations of EOM from RME and HVO combustion particles (<116 ng/ml total PAH) did not cause DNA strand breaks in A549 cells, whereas benzo[a]pyrene and PAH-rich EOM from petrodiesel combusted using low oxygen inlet concentration were genotoxic. The genotoxicity was attributed to high molecular weight PAH isomers with 5-6 rings. In summary, the results show that EOM from the combustion of petrodiesel and RME generate the same level of DNA strand breaks on an equal total PAH basis. However, the genotoxic hazard of engine exhaust from on-road vehicles is lower for RME than petrodiesel because of lower PAH emission per fuel energy content.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"238-249"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119573","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
Current status and future challenges of genotoxicity OECD Test Guidelines for nanomaterials: a workshop report. 经合组织纳米材料基因毒性测试指南的现状和未来挑战:研讨会报告。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-08-24 DOI: 10.1093/mutage/gead017
Shareen H Doak, Cristina Andreoli, Michael J Burgum, Qasim Chaudhry, Eric A J Bleeker, Cecilia Bossa, Josefa Domenech, Damjana Drobne, Valerie Fessard, Nina Jeliazkova, Eleonora Longhin, Elise Rundén-Pran, Maciej Stepnik, Naouale El Yamani, Julia Catalán, Maria Dusinska
{"title":"Current status and future challenges of genotoxicity OECD Test Guidelines for nanomaterials: a workshop report.","authors":"Shareen H Doak,&nbsp;Cristina Andreoli,&nbsp;Michael J Burgum,&nbsp;Qasim Chaudhry,&nbsp;Eric A J Bleeker,&nbsp;Cecilia Bossa,&nbsp;Josefa Domenech,&nbsp;Damjana Drobne,&nbsp;Valerie Fessard,&nbsp;Nina Jeliazkova,&nbsp;Eleonora Longhin,&nbsp;Elise Rundén-Pran,&nbsp;Maciej Stepnik,&nbsp;Naouale El Yamani,&nbsp;Julia Catalán,&nbsp;Maria Dusinska","doi":"10.1093/mutage/gead017","DOIUrl":"10.1093/mutage/gead017","url":null,"abstract":"<p><p>Genotoxicity testing for nanomaterials remains challenging as standard testing approaches require some adaptation, and further development of nano-specific OECD Test Guidelines (TGs) and Guidance Documents (GDs) are needed. However, the field of genotoxicology continues to progress and new approach methodologies (NAMs) are being developed that could provide relevant information on the range of mechanisms of genotoxic action that may be imparted by nanomaterials. There is a recognition of the need for implementation of new and/or adapted OECD TGs, new OECD GDs, and utilization of NAMs within a genotoxicity testing framework for nanomaterials. As such, the requirements to apply new experimental approaches and data for genotoxicity assessment of nanomaterials in a regulatory context is neither clear, nor used in practice. Thus, an international workshop with representatives from regulatory agencies, industry, government, and academic scientists was convened to discuss these issues. The expert discussion highlighted the current deficiencies that exist in standard testing approaches within exposure regimes, insufficient physicochemical characterization, lack of demonstration of cell or tissue uptake and internalization, and limitations in the coverage of genotoxic modes of action. Regarding the latter aspect, a consensus was reached on the importance of using NAMs to support the genotoxicity assessment of nanomaterials. Also highlighted was the need for close engagement between scientists and regulators to (i) provide clarity on the regulatory needs, (ii) improve the acceptance and use of NAM-generated data, and (iii) define how NAMs may be used as part of weight of evidence approaches for use in regulatory risk assessments.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"183-191"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067848","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
Glutathione-related antioxidant defence, DNA damage, and DNA repair in patients suffering from post-COVID conditions. 新冠肺炎后患者的谷胱甘肽相关抗氧化防御、DNA损伤和DNA修复。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-08-24 DOI: 10.1093/mutage/gead021
Selin Kankaya, Fatih Yavuz, Alper Tari, Ahmet Bera Aygun, Esra Gizem Gunes, Bahar Bektan Kanat, Gulru Ulugerger Avci, Hakan Yavuzer, Yildiz Dincer
{"title":"Glutathione-related antioxidant defence, DNA damage, and DNA repair in patients suffering from post-COVID conditions.","authors":"Selin Kankaya,&nbsp;Fatih Yavuz,&nbsp;Alper Tari,&nbsp;Ahmet Bera Aygun,&nbsp;Esra Gizem Gunes,&nbsp;Bahar Bektan Kanat,&nbsp;Gulru Ulugerger Avci,&nbsp;Hakan Yavuzer,&nbsp;Yildiz Dincer","doi":"10.1093/mutage/gead021","DOIUrl":"10.1093/mutage/gead021","url":null,"abstract":"<p><p>Post-COVID conditions are defined as the continuation of the symptoms of Coronavirus Disease 2019 (COVID-19) 3 months after the initial Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, with no other explanation. Post-COVID conditions are seen among 30%-60% of patients with asymptomatic or mild forms of COVID-19. The underlying pathophysiological mechanisms of post-COVID conditions are not known. In SARS-CoV-2 infection, activation of the immune system leads to increased production of reactive oxygen molecules, depleted antioxidant reserve, and finally occurrence of oxidative stress. In oxidative stress conditions, DNA damage increases and DNA repair systems impair. In this study, glutathione (GSH) level, glutathione peroxidase (GPx) activity, 8-hydroxydeoxyguanosine (8-OHdG) level, basal, induced, and post-repair DNA damage were investigated in individuals suffering from post-COVID conditions. In the red blood cells, GSH levels and GPx activities were measured with a spectrophotometric assay and a commercial kit. Basal, in vitro H2O2 (hydrogen peroxide)-induced, and post-repair DNA damage (DNA damage after a repair incubation following H2O2-treatment, in vitro) were determined in lymphocytes by the comet assay. The urinary 8-OHdG levels were measured by using a commercial ELISA kit. No significant difference was found between the patient and control groups for GSH level, GPx activity, and basal and H2O2-induced DNA damage. Post-repair DNA damage was found to be higher in the patient group than those in the control group. Urinary 8-OHdG level was lower in the patient group compared to the control group. In the control group, GSH level and post-repair DNA damage were higher in the vaccinated individuals. In conclusion, oxidative stress formed due to the immune response against SARS-COV-2 may impair DNA repair mechanisms. Defective DNA repair may be an underlying pathological mechanism of post-COVID conditions.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"216-226"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10440312","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
Investigation of genotoxic effect of octyl gallate used as an antioxidant food additive in in vitro test systems. 没食子酸辛酯作为抗氧化食品添加剂在体外试验系统中的遗传毒性研究。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-06-20 DOI: 10.1093/mutage/gead005
Ece Avuloglu Yilmaz, Deniz Yuzbasioglu, Fatma Unal
{"title":"Investigation of genotoxic effect of octyl gallate used as an antioxidant food additive in in vitro test systems.","authors":"Ece Avuloglu Yilmaz,&nbsp;Deniz Yuzbasioglu,&nbsp;Fatma Unal","doi":"10.1093/mutage/gead005","DOIUrl":"https://doi.org/10.1093/mutage/gead005","url":null,"abstract":"Abstract Several antioxidant food additives are added to oils, soups, sauces, chewing gum, potato chips, and so on. One of them is octyl gallate. The purpose of this study was to evaluate the potential genotoxicity of octyl gallate in human lymphocytes, using in vitro chromosomal abnormalities (CA), sister chromatid exchange (SCE), cytokinesis block micronucleus cytome (CBMN-Cyt), micronucleus-FISH (MN-FISH), and comet tests. Different concentrations (0.031, 0.063, 0.125, 0.25, and 0.50 μg/ml) of octyl gallate were used. A negative (distilled water), a positive (0.20 μg/ml Mitomycin-C), and a solvent control (8.77 μl/ml ethanol) were also applied for each treatment. Octyl gallate did not cause changes in chromosomal abnormalities, micronucleus, nuclear bud (NBUD), and nucleoplasmic bridge (NPB) frequency. Similarly, there was no significant difference in DNA damage (comet assay), percentage of centromere positive and negative cells (MN-FISH test) compared to the solvent control. Moreover, octyl gallate did not affect replication and nuclear division index. On the other hand, it significantly increased the SCE/cell ratio in three highest concentrations compared to solvent control at 24 h treatment. Similarly, at 48 h treatment, the frequency of SCE raised significantly compared to solvent controls at all the concentrations (except 0.031 μg/ml). An important reduction was detected in mitotic index values in the highest concentration at 24 h treatment and almost all concentrations (except 0.031 and 0.063 µg/ml) at 48 h treatment. The results obtained suggest that octyl gallate has no important genotoxicological action on human peripheral lymphocytes at the concentrations applied in this study.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 3","pages":"151-159"},"PeriodicalIF":2.7,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9703207","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
Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review. 评价终点的研究和诊断线粒体毒性和疾病:叙述性回顾。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-06-20 DOI: 10.1093/mutage/gead010
Prashamsa Gharti, Jessica F Fletcher, Katherine E Chapman
{"title":"Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review.","authors":"Prashamsa Gharti,&nbsp;Jessica F Fletcher,&nbsp;Katherine E Chapman","doi":"10.1093/mutage/gead010","DOIUrl":"https://doi.org/10.1093/mutage/gead010","url":null,"abstract":"<p><p>Mitochondrial DNA mutation and toxicity have been linked to several inherited and acquired diseases; however, these are challenging to diagnose and characterize due to clinical and genetic heterogeneity. This review investigates current techniques for the analysis of mitochondrial perturbations, and novel, emerging endpoints for routine application within the clinical setting. Particular focus is given to the biochemistry of the mitochondria influencing each endpoint and the relation of these to toxicity. Current approaches such as the use of metabolic markers (e.g. lactate production), and muscle biopsies to measure mitochondrial proteins were found to lack specificity. Newly emerging identified endpoints were: fibroblast growth factor-21, glucose uptake, mitochondrial membrane potential, mitochondrial morphology, mtDNA heteroplasmy, and mutation of mtDNA and nuclear DNA. Owed to the advancement in genetic analysis techniques, it is suggested by this review that genotypic endpoints of mtDNA mutation and heteroplasmy show particular promise as indicators of mitochondrial disease. It is, however, acknowledged that any single endpoint in isolation offers limited information; therefore, it is recommended that analysis of several endpoints simultaneously will offer the greatest benefit in terms of disease diagnosis and study. It is hoped that this review further highlights the need for advancement in understanding mitochondrial disease.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 3","pages":"132-138"},"PeriodicalIF":2.7,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9704698","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
Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes. 橄榄叶提取物和橄榄苦苷功能化Ag NPs对人滋养细胞和外周血淋巴细胞毒性的比较分析。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-06-20 DOI: 10.1093/mutage/gead013
Andrea Pirković, Vesna Lazić, Biljana Spremo-Potparević, Lada Živković, Dijana Topalović, Sanja Kuzman, Jelena Antić-Stanković, Dragana Božić, Milica Jovanović Krivokuća, Jovan M Nedeljković
{"title":"Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes.","authors":"Andrea Pirković,&nbsp;Vesna Lazić,&nbsp;Biljana Spremo-Potparević,&nbsp;Lada Živković,&nbsp;Dijana Topalović,&nbsp;Sanja Kuzman,&nbsp;Jelena Antić-Stanković,&nbsp;Dragana Božić,&nbsp;Milica Jovanović Krivokuća,&nbsp;Jovan M Nedeljković","doi":"10.1093/mutage/gead013","DOIUrl":"https://doi.org/10.1093/mutage/gead013","url":null,"abstract":"<p><p>Dry olive leaf extract (DOLE) and its active component oleuropein (OLE) were applied as reducing and stabilizing agents to prepare colloidal 20-25 nm silver nanoparticles (Ag NPs). The Ag NPs were characterized using transmission electron microscopy, X-ray diffraction analysis, and absorption spectroscopy. The cytotoxic actions of coated Ag NPs, and their inorganic and organic components, were examined against trophoblast cells and human peripheral blood lymphocytes (PBLs), Gram-positive, Gram-negative bacteria, and yeast. The genotoxic potential was evaluated in PBLs in vitro with the comet assay. Ag/DOLE and Ag/OLE induced cytotoxic effects in both types of cells after 24 h exposure when silver concentrations were 0.025-0.2 mM. However, the most pronounced cytotoxicity exhibits Ag/OLE. Both colloids also caused reduced ROS production in both cell types at 0.1 mM and 0.2 mM, while bare Ag NPs did not alter ROS levels at any of the conditions. Functionalized Ag/DOLE and Ag/OLE did not show genotoxic effects in PBLs, while bare AgNPs increased DNA damage significantly only at 0.2 mM. Regarding the antimicrobial effects, the Ag/OLE had MIC values for all evaluated microorganisms from 0.0625 to less than 0.0312 mM. Also, the antimicrobial effect of Ag/DOLE was significantly higher on Gram-negative bacteria and yeast than on Gram-positive bacteria. Obtained results indicate that Ag/OLE induced the most pronounced biological effects, beneficial for its application as an antimicrobial agent, but with potential risks from exposure to high concentrations that could induce cytotoxicity in healthy human cells.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 3","pages":"169-181"},"PeriodicalIF":2.7,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9687699","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
Announcing the UKEMS Next Generation Sequencing special interest group (NGS SIG). 宣布成立UKEMS下一代测序特别兴趣小组(NGS SIG)。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-06-20 DOI: 10.1093/mutage/gead009
Anthony Lynch, Darren Kidd, Anne Ashford
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