Mutagenesis最新文献

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In vitro genotoxicity assessment of French fries from mass catering companies: a preliminary study. 大众餐饮公司炸薯条的体外遗传毒性评价:初步研究。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-02-03 DOI: 10.1093/mutage/geac021
Julen Sanz-Serrano, Roncesvalles Garayoa, Ana Isabel Vitas, Adela López de Cerain, Amaya Azqueta
{"title":"In vitro genotoxicity assessment of French fries from mass catering companies: a preliminary study.","authors":"Julen Sanz-Serrano,&nbsp;Roncesvalles Garayoa,&nbsp;Ana Isabel Vitas,&nbsp;Adela López de Cerain,&nbsp;Amaya Azqueta","doi":"10.1093/mutage/geac021","DOIUrl":"https://doi.org/10.1093/mutage/geac021","url":null,"abstract":"<p><p>It is generally assumed that French fries are likely to have weak in vitro mutagenic activity, but most studies thereof have only assessed gene mutations. In this article, the genotoxicity of 10 extracts of French fries was assessed using the in vitro micronucleus test (following the principles of the OECD 487 guidelines). Each sample was obtained from a different mass catering company in Navarra (Spain). This assay, together with the Ames test, is recommended in the basic in vitro phase included in the European Food Safety Authority Opinion on Genotoxicity Testing Strategies Applicable to Food and Feed Safety Assessment. Eight of 10 samples from mass catering companies induced chromosomal aberrations in the in vitro micronucleus test. Moreover, French fries deep-fried in the laboratory for different periods of time (0, 3, 5, 10, 20, 30 min) were assessed using the in vitro micronucleus test. Genotoxicity was observed in all time periods from 3 min on. The biological relevance of these results must be further explored.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"51-57"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295226","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: 2
Single and combined potential of polystyrene microparticles and fluoranthene in the induction of DNA damage in haemocytes of Mediterranean mussel (Mytilus galloprovincialis). 聚苯乙烯微粒和荧光蒽在地中海贻贝(Mytilus galloprovincialis)血细胞中诱导DNA损伤的单一和联合潜力。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-02-03 DOI: 10.1093/mutage/geac017
Stoimir Kolarević, Margareta Kračun-Kolarević, Jovana Jovanović Marić, Jelena Djordjević, Branka Vuković-Gačić, Danijela Joksimović, Rajko Martinović, Oliver Bajt, Andreja Ramšak
{"title":"Single and combined potential of polystyrene microparticles and fluoranthene in the induction of DNA damage in haemocytes of Mediterranean mussel (Mytilus galloprovincialis).","authors":"Stoimir Kolarević,&nbsp;Margareta Kračun-Kolarević,&nbsp;Jovana Jovanović Marić,&nbsp;Jelena Djordjević,&nbsp;Branka Vuković-Gačić,&nbsp;Danijela Joksimović,&nbsp;Rajko Martinović,&nbsp;Oliver Bajt,&nbsp;Andreja Ramšak","doi":"10.1093/mutage/geac017","DOIUrl":"https://doi.org/10.1093/mutage/geac017","url":null,"abstract":"<p><p>In this study, the possible 'vector effect' within the exposure of Mediterranean mussels (Mytilus galloprovincialis) to polystyrene microplastics with adsorbed fluoranthene was investigated by applying the multibiomarker approach. The major focus was placed on genotoxicological endpoints as to our knowledge there are no literature data on the genotoxicity of polystyrene microparticles alone or with adsorbed fluoranthene in the selected experimental organisms. DNA damage was assessed in haemocytes by comet assay and micronucleus test. For the assessment of neurotoxicity, acetylcholinesterase activity was measured in gills. Glutathione S-transferase was assessed in gills and hepatopancreas since these enzymes are induced for biotransformation and excretion of lipophilic compounds such as hydrocarbons. Finally, differences in physiological response within the exposure to polystyrene particles, fluoranthene, or particles with adsorbed fluoranthene were assessed by the variation of heart rate patterns studied by the noninvasive laser fibre-optic method. The uniform response of individual biomarkers within the exposure groups was not recorded. There was no clear pattern in variation of acetylcholinesterase or glutathione S-transferase activity which could be attributed to the treatment. Exposure to polystyrene increased DNA damage which was detected by the comet assay but was not confirmed by micronucleus formation. Data of genotoxicity assays indicated differential responses among the groups exposed to fluoranthene alone and fluoranthene adsorbed to polystyrene. Change in the heart rate patterns within the studied groups supports the concept of the Trojan horse effect within the exposure to polystyrene particles with adsorbed fluoranthene.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"3-12"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10729196","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
Interspecific differences in oxidative DNA damage after hydrogen peroxide exposure of sea urchin coelomocytes. 过氧化氢暴露后海胆腔瘤细胞氧化DNA损伤的种间差异。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-02-03 DOI: 10.1093/mutage/geac018
Fengjia Liu, Kim S Last, Theodore B Henry, Helena C Reinardy
{"title":"Interspecific differences in oxidative DNA damage after hydrogen peroxide exposure of sea urchin coelomocytes.","authors":"Fengjia Liu,&nbsp;Kim S Last,&nbsp;Theodore B Henry,&nbsp;Helena C Reinardy","doi":"10.1093/mutage/geac018","DOIUrl":"https://doi.org/10.1093/mutage/geac018","url":null,"abstract":"<p><p>Interspecific comparison of DNA damage can provide information on the relative vulnerability of marine organisms to toxicants that induce oxidative genotoxicity. Hydrogen peroxide (H2O2) is an oxidative toxicant that causes DNA strand breaks and nucleotide oxidation and is used in multiple industries including Atlantic salmon aquaculture to treat infestations of ectoparasitic sea lice. H2O2 (up to 100 mM) can be released into the water after sea lice treatment, with potential consequences of exposure in nontarget marine organisms. The objective of the current study was to measure and compare differences in levels of H2O2-induced oxidative DNA damage in coelomocytes from Scottish sea urchins Echinus esculentus, Paracentrotus lividus, and Psammechinus miliaris. Coelomocytes were exposed to H2O2 (0-50 mM) for 10 min, cell concentration and viability were quantified, and DNA damage was measured by the fast micromethod, an alkaline unwinding DNA method, and the modified fast micromethod with nucleotide-specific enzymes. Cell viability was >92% in all exposures and did not differ from controls. Psammechinus miliaris coelomocytes had the highest oxidative DNA damage with 0.07 ± 0.01, 0.08 ± 0.01, and 0.07 ± 0.01 strand scission factors (mean ± SD) after incubation with phosphate-buffered saline, formamidopyrimidine-DNA glycosylase, and endonuclease-III, respectively, at 50 mM H2O2. Exposures to 0.5 mM H2O2 (100-fold dilution from recommended lice treatment concentration) induced oxidative DNA damage in all three species of sea urchins, suggesting interspecific differences in vulnerabilities to DNA damage and/or DNA repair mechanisms. Understanding impacts of environmental genotoxicants requires understanding species-specific susceptibilities to DNA damage, which can impact long-term stability in sea urchin populations in proximity to aquaculture farms.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"13-20"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10785206","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
EEMGS New Investigators: rising stars in environmental mutagenesis. 新研究者:环境诱变的新星。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-02-03 DOI: 10.1093/mutage/geac026
Ezgi Eyluel Bankoglu, Fiona Chapman, Marko Gerić
{"title":"EEMGS New Investigators: rising stars in environmental mutagenesis.","authors":"Ezgi Eyluel Bankoglu,&nbsp;Fiona Chapman,&nbsp;Marko Gerić","doi":"10.1093/mutage/geac026","DOIUrl":"https://doi.org/10.1093/mutage/geac026","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"1-2"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10723027","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
Air pollution in Sarajevo, Bosnia and Herzegovina, assessed by plant comet assay. 用植物彗星测定法评价波斯尼亚和黑塞哥维那萨拉热窝的空气污染。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2023-02-03 DOI: 10.1093/mutage/geac022
Mujo Hasanovic, Tamara Cetkovic, Bertrand Pourrut, Lejla Caluk Klacar, Maida Hadzic Omanovic, Adaleta Durmic-Pasic, Sanin Haveric, Anja Haveric
{"title":"Air pollution in Sarajevo, Bosnia and Herzegovina, assessed by plant comet assay.","authors":"Mujo Hasanovic,&nbsp;Tamara Cetkovic,&nbsp;Bertrand Pourrut,&nbsp;Lejla Caluk Klacar,&nbsp;Maida Hadzic Omanovic,&nbsp;Adaleta Durmic-Pasic,&nbsp;Sanin Haveric,&nbsp;Anja Haveric","doi":"10.1093/mutage/geac022","DOIUrl":"https://doi.org/10.1093/mutage/geac022","url":null,"abstract":"<p><p>Bosnia and Herzegovina (B&H) is among the European countries with the highest rate of air pollution-related death cases and the poorest air quality. The main causes are solid fuel consumption, traffic, and the poorly developed or implemented air pollution reduction policies. In addition, the city of Sarajevo, the capital of B&H, suffers temperature inversion episodes in autumn/winter months, which sustain air pollution. Human biomonitoring studies may be confounded by the lifestyle of subjects or possible metabolic alterations. Therefore, this study aimed to evaluate Ligustrum vulgare L. as a model for air pollution monitoring by measuring DNA damage at one rural and two urban sites. DNA damage was measured as tail intensity (TI) in L. vulgare leaves, considering seasonal, sampling period, leaf position and staging, and spatial (urban versus rural) variation. Effects of COVID-19 lockdown on TI were assessed by periodical monitoring at one of the selected sites, while in-house grown L. vulgare plants were used to test differences between outdoor and indoor air pollution effects for the same sampling period. Significantly higher TI was generally observed in leaves collected in Campus in December 2020 and 2021 compared with March (P < 0.0001). Outer and adult leaves showed higher TI values, except for the rural site where no differences for these categories were found. Leaves collected in the proximity of the intensive traffic showed significantly higher TI values (P < 0.001), regardless of the sampling period and the stage of growth. In regards to the COVID-19 lockdown, higher TI (P < 0.001) was registered in December 2020, after the lockdown period, than in periods before COVID-19 outbreak or immediately after the lockdown in 2020. This also reflects mild air pollution conditions in summer. TI values for the in-house grown leaves were significantly lower compared to those in situ. Results showed that L. vulgare may present a consistent model for the air pollution biomonitoring but further studies are needed to establish the best association between L. vulgare physiology, air quality data, and air pollution effects.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"43-50"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280191","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
The roles of mutated SPINK1 gene in prostate cancer cells. SPINK1基因突变在前列腺癌细胞中的作用。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2022-12-08 DOI: 10.1093/mutage/geac019
Xiuyi Pan, Junya Tan, Xiaoxue Yin, Qianqi Liu, Linmao Zheng, Zhengzheng Su, Qiao Zhou, Ni Chen
{"title":"The roles of mutated SPINK1 gene in prostate cancer cells.","authors":"Xiuyi Pan,&nbsp;Junya Tan,&nbsp;Xiaoxue Yin,&nbsp;Qianqi Liu,&nbsp;Linmao Zheng,&nbsp;Zhengzheng Su,&nbsp;Qiao Zhou,&nbsp;Ni Chen","doi":"10.1093/mutage/geac019","DOIUrl":"https://doi.org/10.1093/mutage/geac019","url":null,"abstract":"<p><p>SPINK1-positive prostate cancer (PCa) has been identified as an aggressive PCa subtype. However, there is a lack of definite studies to elucidate the underlying mechanism of the loss of SPINK1 expression in most PCa cells except 22Rv1 cells, which are derived from a human prostatic carcinoma xenograft, CWR22R. The aim of this study was to investigate the mechanisms of SPINK1 protein positive/negative expression and its biological roles in PCa cell lines. SPINK1 mRNA was highly expressed in 22Rv1 cells compared with LNCaP, C4-2B, DU145, and PC-3 cells, and the protein was only detected in 22Rv1 cells. Among these cell lines, the wild-type SPINK1 coding sequence was only found in 22Rv1 cells, and two mutation sites, the c.194G>A missense mutation and the c.210T>C synonymous mutation, were found in other cell lines. Our further research showed that the mutations were associated with a reduction in SPINK1 mRNA and protein levels. Functional experiments indicated that SPINK1 promoted PC-3 cell proliferation, migration, and invasion, while knockdown of SPINK1 attenuated 22Rv1 cell proliferation, migration, and invasion. The wild-type SPINK1 gene can promote the malignant behaviors of cells more than the mutated ones. Cell cycle analysis by flow cytometry showed that SPINK1 decreased the percentage of cells in the G0/G1 phase and increased the percentage of S phase cells. We demonstrated that the c.194G>A and c.210T>C mutations in the SPINK1 gene decreased the mRNA and protein levels. The wild-type SPINK1 gene is related to aggressive biological behaviors of PCa cells and may be a potential therapeutic target for PCa.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"37 5-6","pages":"238-247"},"PeriodicalIF":2.7,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508234","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
Impact of experimental design factors on the potency of genotoxicants in in vitro tests. 实验设计因素对基因毒物体外试验效力的影响。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2022-12-08 DOI: 10.1093/mutage/geac025
Julie Sanders, Anouck Thienpont, Roel Anthonissen, Tamara Vanhaecke, Birgit Mertens
{"title":"Impact of experimental design factors on the potency of genotoxicants in in vitro tests.","authors":"Julie Sanders,&nbsp;Anouck Thienpont,&nbsp;Roel Anthonissen,&nbsp;Tamara Vanhaecke,&nbsp;Birgit Mertens","doi":"10.1093/mutage/geac025","DOIUrl":"https://doi.org/10.1093/mutage/geac025","url":null,"abstract":"<p><p>Previous studies have shown that differences in experimental design factors may alter the potency of genotoxic compounds in in vitro genotoxicity tests. Most of these studies used traditional statistical methods based on the lowest observed genotoxic effect levels, whereas more appropriate methods, such as the benchmark dose (BMD) approach, are now available to compare genotoxic potencies under different test conditions. We therefore investigated the influence of two parameters, i.e. cell type and exposure duration, on the potencies of two known genotoxicants [aflatoxin B1 and ethyl methanesulfonate (EMS)] in the in vitro micronucleus (MN) assay and comet assay (CA). Both compounds were tested in the two assays using two cell types (i.e. CHO-K1 and TK6 cells). To evaluate the effect of exposure duration, the genotoxicity of EMS was assessed after 3 and 24 h of exposure. Results were analyzed using the BMD covariate approach, also referred to as BMD potency ranking, and the outcome was compared with that of more traditional statistical methods based on lowest observed genotoxic effect levels. When comparing the in vitro MN results obtained in both cell lines with the BMD covariate approach, a difference in potency was detected only when EMS exposures were conducted for 24 h, with TK6 cells being more sensitive. No difference was observed in the potency of both EMS and aflatoxin B1 in the in vitro CA using both cell lines. In contrast, EMS was more potent after 24 h exposure compared with a 3 h exposure under all tested conditions, i.e. in the in vitro MN assay and CA in both cell lines. Importantly, for several of the investigated factors, the BMD covariate method could not be used to confirm the differences in potencies detected with the traditional statistical methods, thus highlighting the need to evaluate the impact of experimental design factors with adequate approaches.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"37 5-6","pages":"248-258"},"PeriodicalIF":2.7,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10799084","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
Ex vivo explant model of adenoma and colorectal cancer to explore mechanisms of action and patient response to cancer prevention therapies. 腺瘤和结直肠癌离体移植模型探讨作用机制和患者对癌症预防治疗的反应。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2022-12-08 DOI: 10.1093/mutage/geac020
Sam Khan, Gareth J Miles, Constantinos Demetriou, Zahirah Sidat, Nalini Foreman, Kevin West, Ankur Karmokar, Lynne Howells, Catrin Pritchard, Anne L Thomas, Karen Brown
{"title":"Ex vivo explant model of adenoma and colorectal cancer to explore mechanisms of action and patient response to cancer prevention therapies.","authors":"Sam Khan,&nbsp;Gareth J Miles,&nbsp;Constantinos Demetriou,&nbsp;Zahirah Sidat,&nbsp;Nalini Foreman,&nbsp;Kevin West,&nbsp;Ankur Karmokar,&nbsp;Lynne Howells,&nbsp;Catrin Pritchard,&nbsp;Anne L Thomas,&nbsp;Karen Brown","doi":"10.1093/mutage/geac020","DOIUrl":"https://doi.org/10.1093/mutage/geac020","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second leading cause of cancer death in the UK. Novel therapeutic prevention strategies to inhibit the development and progression of CRC would be invaluable. Potential contenders include low toxicity agents such as dietary-derived agents or repurposed drugs. However, in vitro and in vivo models used in drug development often do not take into account the heterogeneity of tumours or the tumour microenvironment. This limits translation to a clinical setting. Our objectives were to develop an ex vivo method utilizing CRC and adenoma patient-derived explants (PDEs) which facilitates screening of drugs, assessment of toxicity, and efficacy. Our aims were to use a multiplexed immunofluorescence approach to demonstrate the viability of colorectal tissue PDEs, and the ability to assess immune cell composition and interactions. Using clinically achievable concentrations of curcumin, we show a correlation between curcumin-induced tumour and stromal apoptosis (P < .001) in adenomas and cancers; higher stromal content is associated with poorer outcomes. B cell (CD20+ve) and T cell (CD3+ve) density of immune cells within tumour regions in control samples correlated with curcumin-induced tumour apoptosis (P < .001 and P < .05, respectively), suggesting curcumin-induced apoptosis is potentially predicted by baseline measures of immune cells. A decrease in distance between T cells (CD3+ve) and cytokeratin+ve cells was observed, indicating movement of T cells (CD3+ve) towards the tumour margin (P < .001); this change is consistent with an immune environment associated with improved outcomes. Concurrently, an increase in distance between T cells (CD3+ve) and B cells (CD20+ve) was detected following curcumin treatment (P < .001), which may result in a less immunosuppressive tumour milieu. The colorectal tissue PDE model offers significant potential for simultaneously assessing multiple biomarkers in response to drug exposure allowing a greater understanding of mechanisms of action and efficacy in relevant target tissues, that maintain both their structural integrity and immune cell compartments.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"37 5-6","pages":"227-237"},"PeriodicalIF":2.7,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9115885","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: 1
DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis. 重症COVID-19患者外周血淋巴细胞DNA损伤与炎症标志物和止血参数的关系
IF 2.7 4区 医学
Mutagenesis Pub Date : 2022-10-26 DOI: 10.1093/mutage/geac011
Olgica Mihaljevic,Snezana Zivancevic-Simonovic,Vojislav Cupurdija,Milos Marinkovic,Jovana Tubic Vukajlovic,Aleksandra Markovic,Marijana Stanojevic-Pirkovic,Olivera Milosevic-Djordjevic
{"title":"DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis.","authors":"Olgica Mihaljevic,Snezana Zivancevic-Simonovic,Vojislav Cupurdija,Milos Marinkovic,Jovana Tubic Vukajlovic,Aleksandra Markovic,Marijana Stanojevic-Pirkovic,Olivera Milosevic-Djordjevic","doi":"10.1093/mutage/geac011","DOIUrl":"https://doi.org/10.1093/mutage/geac011","url":null,"abstract":"Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"21 1","pages":"203-212"},"PeriodicalIF":2.7,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518402","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
Optimizing machine-learning models for mutagenicity prediction through better feature selection. 优化机器学习模型,通过更好的特征选择来预测突变性。
IF 2.7 4区 医学
Mutagenesis Pub Date : 2022-10-26 DOI: 10.1093/mutage/geac010
Nicolas K Shinada,Naoki Koyama,Megumi Ikemori,Tomoki Nishioka,Seiji Hitaoka,Atsushi Hakura,Shoji Asakura,Yukiko Matsuoka,Sucheendra K Palaniappan
{"title":"Optimizing machine-learning models for mutagenicity prediction through better feature selection.","authors":"Nicolas K Shinada,Naoki Koyama,Megumi Ikemori,Tomoki Nishioka,Seiji Hitaoka,Atsushi Hakura,Shoji Asakura,Yukiko Matsuoka,Sucheendra K Palaniappan","doi":"10.1093/mutage/geac010","DOIUrl":"https://doi.org/10.1093/mutage/geac010","url":null,"abstract":"Assessing a compound's mutagenicity using machine learning is an important activity in the drug discovery and development process. Traditional methods of mutagenicity detection, such as Ames test, are expensive and time and labor intensive. In this context, in silico methods that predict a compound mutagenicity with high accuracy are important. Recently, machine-learning (ML) models are increasingly being proposed to improve the accuracy of mutagenicity prediction. While these models are used in practice, there is further scope to improve the accuracy of these models. We hypothesize that choosing the right features to train the model can further lead to better accuracy. We systematically consider and evaluate a combination of novel structural and molecular features which have the maximal impact on the accuracy of models. We rigorously evaluate these features against multiple classification models (from classical ML models to deep neural network models). The performance of the models was assessed using 5- and 10-fold cross-validation and we show that our approach using the molecule structure, molecular properties, and structural alerts as feature sets successfully outperform the state-of-the-art methods for mutagenicity prediction for the Hansen et al. benchmark dataset with an area under the receiver operating characteristic curve of 0.93. More importantly, our framework shows how combining features could benefit model accuracy improvements.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"25 1","pages":"191-202"},"PeriodicalIF":2.7,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515849","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
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