Mutagenesis最新文献

{"title":"The Allium cepa comet assay for environmental sample assessment: a scoping review.","authors":"Carlotta Alias, Ilaria Zerbini, Claudia Zani, Donatella Feretti","doi":"10.1093/mutage/geae020","DOIUrl":"10.1093/mutage/geae020","url":null,"abstract":"<p><p>The purposes of this review were to investigate the application of the comet assay in Allium cepa root cells to assess the genotoxicity of environmental samples and to analyse the experimental procedures employed. A literature search was performed selecting articles published between January 2000 and October 2023 from online databases using the combined search terms 'comet assay' and 'A. cepa'. Only 18 papers met the inclusion criteria. None of these were published in the first eight years (2000-2007), highlighting the increasing interest in using the comet assay on A. cepa to analyse environmental samples over the last decade. The majority of the selected studies (15/18, 83%) were performed on samples belonging to the water compartment on onion bulbs. Half of the selected studies (9/18) were conducted to demonstrate the DNA damaging effect of the sample, while the other half of the studies not only recognized the presence of genotoxic agents but also addressed possible remediation measures. Detailed analysis of the experimental procedures revealed heterogeneity in many key steps, such as exposure time, test controls, nuclei isolation solutions, duration of electrophoresis, and number of nuclei scored. This literature review has shown that the comet assay on A. cepa, although recognized as an appropriate tool, is underutilized in environmental toxicology. Greater standardization could lead to its more widespread use, providing valuable information on the genotoxicity of environmental samples and the ability of different processes to mitigate their negative effects on plants.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044061","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}

{"title":"Plasma miR-122-5p and miR-142-5p and their role in chemoresistance of colon cancer patients","authors":"Klara Vokacova, Aneta Landecka, Saba Selvi, Josef Horak, Vendula Novosadova, Katerina Manakova, Miroslav Levy, Veronika Vymetalkova","doi":"10.1093/mutage/geae023","DOIUrl":"https://doi.org/10.1093/mutage/geae023","url":null,"abstract":"Chemoresistance represents a major issue affecting cancer therapy efficacy. Because microRNAs (miRNAs) regulate gene expression on multiple levels, their role in chemoresistance development is reasonably certain. In our previous study, miR-122-5p and miR-142-5p were identified as diagnostic, prognostic, and predictive biomarkers for primary and metastatic rectal cancer. The aim of the present study was to investigate whether these miRNAs can also reflect the disease course of colon cancer (CC) patients. Further, we focused on a deeper understanding of their involvement in 5-fluorouracil (5-FU) chemoresistance development. The expression analysis of both miRNAs was analysed in repeated whole plasma samplings (n=3, approximately every 6 months) of CC patients (n=49) by RT-qPCR. Expression levels of both miRNAs were determined in the 5-FU sensitive and resistant CC cell lines. From RNA-seq profiles of both sensitive and 5-FU resistant DLD-1 cell lines, the expression levels of miR-122-5p and miR-142-5p validated target genes were detected and compared. Significant differences in the expression levels of both miRNAs between T0 and T1 or T2 samplings were observed. Further, an association between the occurrence of relapse and miR-122-5p expression levels was noticed. Patients who did not relapse had higher expression of miR-122-5p at T1 (p=0.01; 3.16-fold change) and T2 (p=0.04; 2.79-fold change) samplings in comparison with T0 sampling. Out of all miR-122-5p validated targets (n=102), 25 genes were significantly differentially expressed between sensitive and 5-FU-resistant cell lines. Our data suggest that miR-122-5p may represent a predictive marker of tumour relapse in CC patients. In vitro data suggests that this aspect may be linked to the potential therapeutic targets of miR-122-5p related to 5-FU-based chemoresistance. However, deeper mechanistic studies are still needed for progress toward personalized medicine.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253259","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}

{"title":"Exploring the Relationship Between Genetic Instability and Health Outcomes in Acute and Chronic Post-COVID Syndrome.","authors":"Bruna Alves Alonso Martins, Ana Leticia Hilario Garcia, Malu Siqueira Borges, Juliana Picinini, Enaile Tuliczewski Serpa, Daiane Dias Ribeiro Nobles, Luana Letícia Silva, Daiana Dalberto, Alana Witt Hansen, Fernando Rosado Spilki, Lavínia Schuler-Faccini, Pabulo Henrique Rampelotto, Juliana da Silva","doi":"10.1093/mutage/geae022","DOIUrl":"https://doi.org/10.1093/mutage/geae022","url":null,"abstract":"<p><p>The COVID-19 pandemic has led to the emergence of acute and chronic post-COVID syndromes, which present diverse clinical manifestations. The underlying pathophysiology of these conditions is not yet fully understood, but genetic instability has been proposed as a potential contributing factor. This study aimed to explore the differential impact of physical and psychological health factors on genetic instability in individuals with acute and chronic post-COVID syndromes. In this study, three groups of subjects were analyzed: a control group, an acute post-COVID group, and a chronic post-COVID group, with a total of 231 participants. The participants were assessed using a questionnaire for long-COVID-19COVID, and female participants reported more symptoms than male participants in areas related to fatigue, memory, mental health, and well-being during the chronic phase. Genetic instability was assessed using the comet assay, and participants' physical and psychological profiles were evaluated. The overall results showed no significant differences in DNA damage, as measured by the comet assay, among the three groups, suggesting that genetic instability, as assessed by this method, may not be a primary driver of the distinct clinical presentations observed in post-COVID syndromes. However, when gender was considered, male participants in the acute long COVID group exhibited higher levels of genetic instability compared to females. Multiple linear regression analysis revealed that gender, age, and waist circumference were significant predictors of DNA damage. Among females in the acute group, sexual health, and eye-related symptoms significantly influenced the increase in DNA damage. These findings indicate the need for further investigation on the gender-specific differences in genetic instability and their potential implications for the pathophysiology of post-COVID syndromes. Exploring alternative markers of genetic instability and the interplay between genetic, inflammatory, and cellular processes could provide valuable insights for the management of these debilitating post-viral sequelae.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109654","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}

{"title":"Determination of global DNA methylation level by methylation-sensitive comet assay in patients with urinary bladder cancer.","authors":"Özer Koçak, Selin Kankaya, Göktuğ Kalender, Sinharib Citgez, Bülent Önal, Yıldız Dinçer","doi":"10.1093/mutage/geae018","DOIUrl":"https://doi.org/10.1093/mutage/geae018","url":null,"abstract":"<p><p>DNA methylation is an important mechanism in the regulation of gene expression and maintenance of genomic integrity. Aberrant DNA methylation is an early event in carcinogenesis. DNA methyltransferase inhibitors are used to restore aberrant DNA methylation and inhibit tumor growth. Evaluation of DNA methylation level is important for an effective anti-cancer therapy. In the present study, the determination of global DNA methylation levels in patients with urinary bladder cancer was proposed. The methylation-sensitive comet assay determined the global DNA methylation level at the level of single cells. McrBC enzyme, a methylation-sensitive restriction endonuclease was used for enzymatic digestion to generate additional breaks at methylated sites. % DNA methylation level was significantly higher in patients with bladder cancer compared to the control group. The clinical performance of % DNA methylation analysis by methylation-sensitive comet assay was evaluated by ROC curve. Using the cut-off value of 6,5% DNA methylation, 92% sensitivity, and 42% specificity were obtained. In conclusion, global DNA methylation measured by methylation-sensitive comet assay may be a promising non-invasive biomarker that reduces interventional tests required in the diagnosis and follow-up of urinary bladder cancer.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913317","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}

{"title":"Cyto- and genotoxicity evaluation of water samples collected from two rivers in the Kosovo.","authors":"Fisnik H Asllani, Avdulla J Alija, Peter M Eckl, Nikolaus Bresgen","doi":"10.1093/mutage/geae019","DOIUrl":"https://doi.org/10.1093/mutage/geae019","url":null,"abstract":"<p><p>River water in Kosovo is exposed to various discharges from industrial and agricultural activities as well as to urban wastewater. Rivers Sitnica and Drenica are among the most affected ones and water samples drawn from these rivers show the presence of various toxic substances. Genotoxic effects are seen in fish living in these rivers indicating a cytotoxic and mutagenic potential of the river water. Aiming at substantiating these observations, we assessed cyto- and genotoxic effects of water samples collected at different locations from Drenica and Sitnica river. Samples drawn from Lake Badovc served for comparison. To address seasonal effects, samples were collected at different seasons/time points during the period summer 2016 - spring 2018. The water samples were analyzed employing primary rat hepatocytes as reliable in vitro cell model for the assessment of cytotoxic effects (mitotic arrest and cell death) and DNA damage/genotoxicity (micronucleus assay, Comet assay). The results do not account for significant effects associated with specific locations but demonstrate seasonal differences of the genotoxic potential of the water samples collected along both rivers, which are accompanied by a limited cytotoxic potential. Our data provide substantial support to earlier observations and strongly warrant the need for continuous chemical as well as biological monitoring of the river water in Kosovo, focusing on an improved toxicant profiling of the river water and investigations addressing the observed seasonal variations.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907078","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}

{"title":"Dihydroquercetin and biochaga reduce H2O2 induced DNA damage in peripheral blood mononuclear cells of obese women in vitro-a pilot study.","authors":"Lada Živković, Andrea Pirković, Dijana Topalović, Sunčica Borozan, Vladan Bajić, Vesna Dimitrijević Srećković, Ninoslav Djelić, Hristina Petrović, Mirta Milić, Biljana Spremo-Potparević","doi":"10.1093/mutage/geae017","DOIUrl":"https://doi.org/10.1093/mutage/geae017","url":null,"abstract":"<p><p>Systemic oxidative stress stemming from increased free radical production and reduced antioxidant capacity are common characteristics of obese individuals. Using hydrogen peroxide (H2O2) to induce DNA damage in vitro, in peripheral blood mononuclear cells (PBMCs) from obese subjects and controls, the DNA protective ability of dihidroqercetin (DHQ) and biochaga (B) alone or in combination, were evaluated. The effects of DHQ and B were estimated under two experimental conditions: pre-treatment, where cells were pre-incubated with the substances prior to H2O2 exposure; and post-treatment when cells were first exposed to H2 H2O2, and further treated with the compounds. DNA damage was evaluated using the comet assay. The results of pre- and post-treatment showed a significant decrease in DNA damage produced by H2O2 in the obese group. This decrease was not significant in control group probably due to a small number of subjects in this pilot study. More prominent attenuation was noted in the pre-treatment with DHQ (250 μg/mL). Analysis of antioxidant properties revealed that DHQ's remarkable reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, and potent ∙OH scavenging properties may contribute to strong attenuation of H2O2 induced DNA damage. Also, B showed strong reducing power, DPPH, and ∙OH scavenging ability, while reducing power and DPPH scavenger effects were increased in the presence of DHQ. Conclusively, DHQ and B may reduce H2O2-induced DNA damage in PBMCs from obese subjects when challenged in vitro, and could be valuable tools in future research against oxidative damage-related conditions.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633980","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}

{"title":"Expression of Concern: Divergent molecular profile of PIK3CA gene in arsenic-associated bladder carcinoma.","authors":"","doi":"10.1093/mutage/geae016","DOIUrl":"10.1093/mutage/geae016","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545047","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}

{"title":"Fecal miRNA profiles in colorectal cancers with mucinous morphology.","authors":"Alessio Naccarati, Mihnea P Dragomir, Sonia Tarallo, Amedeo Gagliardi, Virginia Alberini, Tomas Buchler, Vaclav Liska, Gaetano Gallo, Veronika Vymetalkova, Ludmila Vodickova, Pavel Vodicka, Barbara Pardini, Giulio Ferrero","doi":"10.1093/mutage/geae015","DOIUrl":"https://doi.org/10.1093/mutage/geae015","url":null,"abstract":"<p><p>Diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this subtype is still a matter of debate. In this study, we investigated whether stool miRNA profiles of CRC patients differ in patients with mucinous histopathological subtypes compared to non-mucinous cancers. In this respect, we also explored how the stool miRNA signature reported in our previous multicentric study (Pardini et al., Gastroenterology 2023) behave in this histotype. Small-RNA sequencing was performed in fecal and tissue samples of an Italian cohort (n=172), including 27 CRC with mucinous morphology (mucinous cancers with >50% mucinous morphology and those with mucinous component >5% but <50%), 58 non-mucinous CRC, and 87 colonoscopy-negative controls. Results were compared with fecal miRNA profiles of a cohort from the Czech Republic (n=98). Most of the differentially expressed (DE) stool miRNAs (n=324) were in common between CRC with mucinous morphology and non-mucinous histopathological subtypes in comparison with healthy controls. Interestingly, the altered levels of 25 fecal miRNAs previously identified distinguishing CRC cases from controls in both cohorts were also confirmed after stratification for mucinous morphology. Forty-nine miRNAs were DE exclusively in CRC with mucinous morphology and 61 in non-mucinous CRC. Mucinous cancers and those with mucinous component showed fairly similar profiles that were comparable in the Czech cohort. Among the stool DE miRNAs observed in CRC with mucinous morphology, 20 were also altered in the comparison between tumor and adjacent mucosa tissue. This study highlights miRNAs specifically altered in CRC with mucinous morphology. Nevertheless, the performance of our stool miRNA signature in accurately distinguishing CRC cases from controls was not significantly affected by this histological subtype. This aspect further supports the use of stool miRNAs for noninvasive diagnosis and screening strategies.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284215","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}

{"title":"Incidental Germline Findings During Comprehensive Genomic Profiling of Pancreatic and Colorectal Cancer: Single-center, Molecular Tumor Board Experience.","authors":"Michal Eid, Jakub Trizuljak, Renata Taslerova, Martin Gryc, Jakub Vlazny, Sara Vilmanova, Martina Jelinkova, Alena Homolova, Stepan Tucek, Jan Hlavsa, Tomas Grolich, Zdenek Kala, Zdenek Kral, Ondrej Slaby","doi":"10.1093/mutage/geae014","DOIUrl":"https://doi.org/10.1093/mutage/geae014","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076262","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}

{"title":"Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway.","authors":"Danah Almohdar, Pradnya Kamble, Chandrakala Basavannacharya, Mitchell Gulkis, Ozlem Calbay, Shuang Huang, Satya Narayan, Melike Çağlayan","doi":"10.1093/mutage/geae013","DOIUrl":"https://doi.org/10.1093/mutage/geae013","url":null,"abstract":"<p><p>DNA ligase (LIG) I and IIIα finalize base excision repair (BER) by sealing a nick product after nucleotide insertion by DNA polymerase (pol) β at the downstream steps. We previously demonstrated that a functional interplay between polβ and BER ligases is critical for efficient repair, and polβ mismatch or oxidized nucleotide insertions confound final ligation step. Yet, how targeting downstream enzymes with small molecule inhibitors could affect this coordination remains unknown. Here, we report that DNA ligase inhibitors, L67 and L82-G17, slightly enhance hypersensitivity to oxidative stress-inducing agent, KBrO3, in polβ+/+ cells more than polβ-/- null cells. We showed less efficient ligation after polβ nucleotide insertions in the presence of the DNA ligase inhibitors. Furthermore, the mutations at the ligase inhibitor binding sites (G448, R451, A455) of LIG1 significantly affect nick DNA binding affinity and nick sealing efficiency. Finally, our results demonstrated that the BER ligases seal a gap repair intermediate by the effect of polβ inhibitor that diminishes gap filling activity. Overall, our results contribute to understand how the BER inhibitors against downstream enzymes, polβ, LIG1, and LIGIIIα, could impact the efficiency of gap filling and subsequent nick sealing at the final steps leading to the formation of deleterious repair intermediates.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912533","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}