Mutagenesis最新文献

{"title":"Impact of cigarette smoking on genetic stability, cell division and cytotoxicity in buccal cells of old and young woman.","authors":"Armen Nersesyan, Michael Kundi, Rafayel Muradyan, Georg Wultsch, Miroslav Misik, Franziska Ferk, Siegfried Knasmueller","doi":"10.1093/mutage/geaf003","DOIUrl":"https://doi.org/10.1093/mutage/geaf003","url":null,"abstract":"<p><p>We investigated the impact of cigarette smoking, daily exposure to tar and nicotine, and the duration of smoking on genetic instability (chromosomal damage - micronuclei, MN, nuclear buds - gene amplification) as well as on disturbances in mitosis (resulting in binucleated cells). Furthermore, we analyzed markers of cytotoxic effects (such as the formation of condensed chromatin, pyknotic, karyolytic, and karyorrhectic cells) and the mitotic activity of the oral mucosa. These parameters were monitored in groups of old (postmenopausal) and young (premenopausal) smoking and non-smoking women (n= 25/group). We found no differences of the MN frequencies in the non-smoking groups and only a moderate (not significant) increase of MN in both groups of smokers. However, we observed a clear increase of markers of genomic instability in both smoking groups. Furthermore, the mitotic activity of cells in the mucosa and of anomalies caused by acute cytotoxicty was higher in both smoking groups. Nicotine uptake was associated with pronounced acute toxic effects and increased the cell division rate. Chromosomal damage (MN) was higher in individuals which consumed high amounts of tar (this effect was not significant) and caused moderate acute toxicity. Our findings indicate (i) that age and hormonal status have no strong impact on the genotoxic and cytotoxic effects in smoking women, (ii) consumption of up to 30 cigarettes/day does not cause chromosomal damage in buccal cells, however positive results were found in earlier studies in heavy smokers, (iii) smoking increased markers which reflect genetic instability and the division rate of oral mucosa cells. These effects may play a role in neoplastic transformation of cells in the upper respiratory tract in smokers. The duration of smoking was associated with a slight (not significant) increase of the mitotic activity and of chromosomal damage and with moderate acute cytotoxicity.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189832","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":"Tribute to Professor Diana Anderson: A scientist extra ordinaire (11.12.1940 - 11.10.2024).","authors":"Alok Dhawan","doi":"10.1093/mutage/geaf002","DOIUrl":"https://doi.org/10.1093/mutage/geaf002","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008608","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":"Maternal exercise before and during pregnancy protects against genotoxicity and promotes offspring hippocampal health in mice prenatally exposed to high fructose.","authors":"Marina Lummertz Magenis, Isadora de Oliveira Monteiro, Adriani Paganini Damiani, Ligia Salvan Dagostin, Otávio Lúcio Possamai, Eduarda Behenck Medeiros, Josiane Budni, João Vitor Silvano Bittencourt, Carolini Mendes, Paulo Cesar Lock Silveira, Ana Letícia Hilario Garcia, Juliana da Silva, Wanessa de Feveri, Sabine A S Langie, Roger Godschalk, Vanessa Moraes de Andrade","doi":"10.1093/mutage/geaf001","DOIUrl":"https://doi.org/10.1093/mutage/geaf001","url":null,"abstract":"<p><p>The fetal brain is susceptible to programming effects during pregnancy, potentially leading to long-term consequences for offspring's cognitive health. Fructose intake is thought to adversely affect fetal brain development, whereas physical exercise before and during pregnancy may be protective. Therefore, this study aimed to assess biochemical and genotoxic changes in maternal hippocampi and behavioral, genotoxic, and biochemical alterations in offspring hippocampi. Seventy female mice were exposed to fructose (20%/L) and/or voluntary physical exercise (VPE) pre-pregnancy for eight weeks, and then mated and exposure was continued until weaning. Offspring were evaluated at 60 days old using behavioral test, genotoxic and biochemical markers. Fructose induced long-term memory impairment in male offspring, which was alleviated by VPE. VPE mitigated DNA damage from maternal fructose consumption in both maternal and offspring hippocampi in female offspring, VPE increased levels of APE-1, NRF2, and CREB proteins, whereas in males, OGG1 levels upregulate. Fructose consumption led to oxidative stress and antioxidant defense alterations in offspring, while VPE mitigated these effects. Telomere shortening was observed in male offspring from mothers who consumed fructose during pregnancy. Our findings suggest that exposure to fructose during (pre)pregnancy and lactation has adverse effects on offspring's hippocampi later in life, and VPE has a protective effect. Overall, the study underscores the significance of maternal dietary and physical habits on long term offspring health, with an emphasis on implications for adult cognitive function.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971678","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":"A pooled analysis of host factors that affect nucleotide excision repair in humans.","authors":"Congying Zheng, Sergey Shaposhnikov, Andrew Collins, Gunnar Brunborg, Amaya Azqueta, Sabine A S Langie, Maria Dusinka, Jana Slyskova, Pavel Vodicka, Frederik-Jan van Schooten, Stefano Bonassi, Mirta Milic, Irene Orlow, Roger Godschalk","doi":"10.1093/mutage/geae028","DOIUrl":"https://doi.org/10.1093/mutage/geae028","url":null,"abstract":"<p><p>Nucleotide excision repair (NER) is crucial for repairing bulky lesions and crosslinks in DNA caused by exogenous and endogenous genotoxins. The number of studies that have considered DNA repair as a biomarker is limited, and therefore one of the primary objectives of the European COST Action hCOMET (CA15132) was to assemble and analyze a pooled database of studies with data on NER activity. The database comprised 738 individuals, gathered from 5 laboratories that ran population studies using the comet-based in vitro DNA repair assay. NER activity data in peripheral blood mononuclear cells (PBMCs) were normalized and correlated with various host-related factors, including sex, age, body mass index (BMI), and smoking habits. This multifaceted analysis uncovered significantly higher NER activity in female participants compared to males (1.08 ± 0.74 vs. 0.92 ± 0.71; P = 0.002). Higher NER activity was seen in older subjects (> 30 years), and the effect of age was most pronounced in the oldest females, particularly those over 70 years (P = 0.001). Females with a normal BMI (< 25 kg/m2) exhibited the highest levels of NER, whereas the lowest NER was observed in overweight males (BMI ≥ 25 kg/m2). No independent effect of smoking was found. After stratification by sex and BMI, higher NER was observed in smoking males (P = 0.017). The biological implication of higher or lower repair capacity remains unclear; the inclusion of DNA repair as a biomarker in molecular epidemiological trials should elucidate the link between health and disease status.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818626","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":"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":" ","pages":"287-300"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","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":"Piper auritum ethanol extract is a potent antimutagen against food-borne aromatic amines: mechanisms of action and chemical composition.","authors":"Sandra L Hernández-Ojeda, Javier Jesús Espinosa-Aguirre, Rafael Camacho-Carranza, Jessica Amacosta-Castillo, Ricardo Cárdenas-Ávila","doi":"10.1093/mutage/geae011","DOIUrl":"10.1093/mutage/geae011","url":null,"abstract":"<p><p>An ethanol extract of Piper auritum leaves (PAEE) inhibits the mutagenic effect of three food-borne aromatic amines (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)) in the TA98 Salmonella typhimurium strain. Preincubation with MeIQx demonstrated in mutagenesis experiments that inhibition of Cytochrome P450 (CYP), as well as direct interaction between component(s) of the plant extract with mutagens, might account for the antimutagenic observed effect. Gas chromatography/mass spectrometry analysis revealed that safrole (50.7%), α-copaene (7.7%), caryophyllene (7.2%), β-pinene (4.2%), γ-terpinene (4.1%), and pentadecane (4.1%) as the main components (PAEE). Piper extract and safrole were able to inhibit the rat liver microsomal CYP1A1 activity that participates in the amines metabolism, leading to the formation of the ultimate mutagenic/ molecules. According to this, safrole and PAEE-inhibited MeIQx mutagenicity but not that of the direct mutagen 2-nitrofluorene. No mutagenicity of plant extract or safrole was detected. This study shows that PAEE and its main component safrole are associated with the inhibition of heterocyclic amines activation due in part to the inhibition of CYP1A subfamily activity.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"301-309"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194216","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}

{"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":"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 the cyto- and genotoxic effects of water samples collected at different locations from the Drenica and Sitnica rivers. Samples drawn from Lake Badovc served for comparison. To address seasonal effects, samples were collected at different seasons/time points during the period of summer 2016-spring 2018. The water samples were analyzed employing primary rat hepatocytes as a reliable in vitro cell model for the assessment of cytotoxic effects (mitotic arrest and cell death) and DNA damage/genotoxicity (micronucleus assay and 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 improved toxicant profiling of the river water and investigations addressing the observed seasonal variations.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"310-317"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","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":"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":" ","pages":"327"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","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":"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":"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 the 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":" ","pages":"263-279"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529620/pdf/","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":"OA","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":"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":" ","pages":"318-326"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","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}