Mutation Research-Reviews in Mutation Research最新文献

{"title":"DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol","authors":"Moon-shong Tang ,&nbsp;Hyun-Wook Lee ,&nbsp;Mao-wen Weng ,&nbsp;Hsiang-Tsui Wang ,&nbsp;Yu Hu ,&nbsp;Lung-Chi Chen ,&nbsp;Sung-Hyun Park ,&nbsp;Huei-wei Chan ,&nbsp;Jiheng Xu ,&nbsp;Xue-Ru Wu ,&nbsp;He Wang ,&nbsp;Rui Yang ,&nbsp;Karen Galdane ,&nbsp;Kathryn Jackson ,&nbsp;Annie Chu ,&nbsp;Elizabeth Halzack","doi":"10.1016/j.mrrev.2021.108409","DOIUrl":"10.1016/j.mrrev.2021.108409","url":null,"abstract":"<div><p>The allure of tobacco smoking is linked to the instant gratification provided by inhaled nicotine. Unfortunately, tobacco curing and burning generates many mutagens including more than 70 carcinogens. There are two types of mutagens and carcinogens in tobacco smoke (TS): direct DNA damaging carcinogens and procarcinogens, which require metabolic activation to become DNA damaging. Recent studies provide three new insights on TS-induced DNA damage. First, two major types of TS DNA damage are induced by direct carcinogen aldehydes, cyclic-1,<em>N²</em>-hydroxy-deoxyguanosine (γ-OH-PdG) and α-methyl-1, <em>N²</em>-γ-OH-PdG, rather than by the procarcinogens, polycyclic aromatic hydrocarbons and aromatic amines. Second, TS reduces DNA repair proteins and activity levels. TS aldehydes also prevent procarcinogen activation. Based on these findings, we propose that aldehydes are major sources of TS induce DNA damage and a driving force for carcinogenesis. E-cigarettes (E-cigs) are designed to deliver nicotine in an aerosol state, without burning tobacco. E-cigarette aerosols (ECAs) contain nicotine, propylene glycol and vegetable glycerin. ECAs induce O⁶-methyl-deoxyguanosines (O⁶-medG) and cyclic γ-hydroxy-1,<em>N²</em><span>--propano-dG (γ-OH-PdG) in mouse lung, heart and bladder tissues and causes a reduction of DNA repair proteins and activity in lungs. Nicotine and nicotine-derived nitrosamine ketone (NNK) induce the same types of DNA adducts and cause DNA repair inhibition in human cells. After long-term exposure, ECAs induce lung adenocarcinoma and bladder urothelial hyperplasia in mice. We propose that E-cig nicotine can be nitrosated in mouse and human cells becoming nitrosamines, thereby causing two carcinogenic effects, induction of DNA damage and inhibition of DNA repair, and that ECA is carcinogenic in mice. Thus, this article reviews the newest literature on DNA adducts and DNA repair inhibition induced by nicotine and ECAs in mice and cultured human cells, and provides insights into ECA carcinogenicity in mice.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108409"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10807812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of mentoring in the careers of geneticists","authors":"Elof Axel Carlson","doi":"10.1016/j.mrrev.2022.108417","DOIUrl":"10.1016/j.mrrev.2022.108417","url":null,"abstract":"<div><p>This commentary reflects on the importance of mentoring in science education. It is written from the perspective of a geneticist and historian of science, but its implications extend to many other fields. A lineage of mentoring is traced from the author's educational experience back through several centuries in the form of an intellectual pedigree.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108417"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49430184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation","authors":"Olivia Solomon ,&nbsp;Karen Huen ,&nbsp;Paul Yousefi ,&nbsp;Leanne K. Küpers ,&nbsp;Juan R. González ,&nbsp;Matthew Suderman ,&nbsp;Sarah E. Reese ,&nbsp;Christian M. Page ,&nbsp;Olena Gruzieva ,&nbsp;Peter Rzehak ,&nbsp;Lu Gao ,&nbsp;Kelly M. Bakulski ,&nbsp;Alexei Novoloaca ,&nbsp;Catherine Allard ,&nbsp;Irene Pappa ,&nbsp;Maria Llambrich ,&nbsp;Marta Vives ,&nbsp;Dereje D. Jima ,&nbsp;Tuomas Kvist ,&nbsp;Andrea Baccarelli ,&nbsp;Nina Holland","doi":"10.1016/j.mrrev.2022.108415","DOIUrl":"10.1016/j.mrrev.2022.108415","url":null,"abstract":"<div><h3>Background</h3><p>Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.</p></div><div><h3>Methods</h3><p>We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268).</p></div><div><h3>Results</h3><p>In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (<em>p</em> &lt; 1.3 × 10⁻⁷) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (<em>p</em> &lt; 1.1 × 10⁻⁶) in older children and had methylation differences in the same direction.</p></div><div><h3>Conclusions</h3><p>This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108415"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623595/pdf/nihms-1829703.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9150913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotoxicity evaluation of medical devices: A regulatory perspective","authors":"Tirukalikundram S. Kumaravel ,&nbsp;Tiruvathipuram N. Sathya ,&nbsp;Ramalingam Balaje ,&nbsp;Pitchaipillai Pradeepa ,&nbsp;Desikan Yogaraj ,&nbsp;Malliga R. Murali ,&nbsp;K.R. Navaneethakrishnan ,&nbsp;Sivasubramanian Murugan ,&nbsp;Awadhesh N. Jha","doi":"10.1016/j.mrrev.2021.108407","DOIUrl":"10.1016/j.mrrev.2021.108407","url":null,"abstract":"<div><p><span>This review critically evaluates our current regulatory understanding of genotoxicity testing and risk assessment of medical devices. Genotoxicity risk assessment of these devices begins with the evaluation of materials of construction, manufacturing additives and all residual materials for potential to induce DNA damage. This is followed by extractable and/or leachable (E&amp;L) studies to understand the worst case and/or clinical exposures, coupled with risk assessment of extractables or leachables. The TTC (Threshold of Toxicological Concern) approach is used to define acceptable levels of genotoxic chemicals, when identified. Where appropriate, </span><em>in silico</em> predictions may be used to evaluate the genotoxic potentials of identifiable chemicals with limited toxicological data and above the levels defined by TTC. Devices that could not be supported by E&amp;L studies are evaluated by <em>in vitro</em><span> genotoxicity studies conducted in accordance with ISO10993-3 and 33. Certain endpoints such as ‘site of contact genotoxicity’ that are specific for certain classes of medical devices are currently not addressed in the current standards. The review also illustrates the potential uses of recent advances to achieve the goal of robust genotoxicity assessment of medical devices which are being increasingly used for health benefits. The review also highlights the gaps for genotoxicity risk assessment of medical devices and suggests possible approaches to address them taking into consideration the recent advances in genotoxicity testing including their potential uses in biocompatibility assessment.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108407"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42533687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of hypoxanthine guanine phosphoribosyltransferase mutant T cells in human blood: The concept of surrogate selection for immunologically relevant cells","authors":"Noah A. Kaitz ,&nbsp;Cindy L. Zuleger ,&nbsp;Peng Yu ,&nbsp;Michael A. Newton ,&nbsp;Richard J. Albertini ,&nbsp;Mark R. Albertini","doi":"10.1016/j.mrrev.2022.108414","DOIUrl":"10.1016/j.mrrev.2022.108414","url":null,"abstract":"<div><p><span><span>Somatic cell </span>gene mutations<span><span><span> arise in vivo due to replication errors during DNA synthesis<span> occurring spontaneously during normal DNA synthesis or as a result of replication on a DNA template damaged by endogenous or exogenous </span></span>mutagens<span>. In principle, changes in the frequencies of mutant cells in vivo in humans reflect changes in exposures to exogenous or endogenous DNA damaging insults, other factors being equal. It is becoming increasingly evident however, that </span></span>somatic mutations<span><span> in humans have a far greater range of interpretations. For example, mutations in lymphocytes provide invaluable probes for in vivo cellular and molecular processes, providing identification of clonal amplifications of these cells in autoimmune and infectious diseases, transplantation recipients, paroxysmal nocturnal hemoglobinuria (PNH), and cancer. The assay for mutations of the X-chromosomal hypoxanthine </span>guanine phosphoribosyltransferase (</span></span></span><em>HPRT</em>) gene has gained popular acceptance for this purpose since viable mutant cells can be recovered for molecular and other analyses. Although the major application of the <em>HPRT</em><span> T cell assay remains human population monitoring, the enrichment of activated T cells in the mutant fraction in individuals with ongoing immunological processes has demonstrated the utility of surrogate selection, a method that uses somatic mutation as a surrogate marker for the in vivo T cell proliferation that underlies immunological processes to investigate clinical disorders with immunological features. Studies encompassing a wide range of clinical conditions are reviewed. Despite the historical importance of the </span><em>HPRT</em> mutation system in validating surrogate selection, there are now additional mutational and other methods for identifying immunologically active T cells. These methods are reviewed and provide insights for strategies to extend surrogate selection in future studies.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108414"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9454872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of COVID-19 in the induction of DNA damage","authors":"Pablo Pánico,&nbsp;Patricia Ostrosky-Wegman,&nbsp;Ana María Salazar","doi":"10.1016/j.mrrev.2022.108411","DOIUrl":"10.1016/j.mrrev.2022.108411","url":null,"abstract":"<div><p>The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is challenging global health and economic systems. In some individuals, COVID-19 can cause a wide array of symptoms, affecting several organs, such as the lungs, heart, bowels, kidneys and brain, causing multiorgan failure, sepsis and death. These effects are related in part to direct viral infection of these organs, immunological deregulation, a hypercoagulatory state and the potential for development of cytokine storm syndrome. Since the appearance of COVID-19 is recent, the long-term effects on the health of recovered patients remain unknown. In this review, we focused on current evidence of the mechanisms of DNA damage mediated by coronaviruses. Data supports that these viruses can induce DNA damage, genomic instability, and cell cycle deregulation during their replication in mammalian cells. Since the induction of DNA damage and aberrant DNA repair mechanisms are related to the development of chronic diseases such as cancer, diabetes, neurodegenerative disorders, and atherosclerosis, it will be important to address similar effects and outcomes in recovered COVID-19 patients.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108411"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10811554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Micronuclei and Disease” special issue: Aims, scope, and synthesis of outcomes","authors":"Michael Fenech ,&nbsp;Siegfried Knasmueller ,&nbsp;Lisbeth E. Knudsen ,&nbsp;Micheline Kirsch-Volders ,&nbsp;Permal Deo ,&nbsp;Bernhard Franzke ,&nbsp;Helga Stopper ,&nbsp;Maria-Grazia Andreassi ,&nbsp;Claudia Bolognesi ,&nbsp;Varinderpal S. Dhillon ,&nbsp;Blanca Laffon ,&nbsp;Karl-Heinz Wagner ,&nbsp;Stefano Bonassi","doi":"10.1016/j.mrrev.2021.108384","DOIUrl":"10.1016/j.mrrev.2021.108384","url":null,"abstract":"<div><p>The purpose of the “Micronuclei and Disease” special issue (SI) is to: (i) Determine the level of evidence for association of micronuclei (MN), a biomarker of numerical and structural chromosomal aberrations, with risk of specific diseases in humans; (ii) Define plausible mechanisms that explain association of MN with each disease; (iii) Identify knowledge gaps and research needed to translate MN assays into clinical practice.</p><p>The “MN and Disease” SI includes 14 papers. The first is a review of mechanisms of MN formation and their consequences in humans. 11 papers are systematic reviews and/or meta-analyses of the association of MN with reproduction, child health, inflammation, auto-immune disease, glycation, metabolic diseases, chronic kidney disease, cardiovascular disease, eleven common cancers, ageing and frailty. The penultimate paper focuses on effect of interventions on MN frequency in the elderly. A road map for translation of MN data into clinical practice is the topic of the final paper.</p><p>The majority of reviewed studies were case-control studies in which the ratio of mean MN frequency in disease cases relative to controls, i.e. the mean ratio (MR), was calculated. The mean of these MR values, estimated by meta-analyses, for lymphocyte and buccal cell MN in non-cancer diseases were 2.3 and 3.6 respectively, and for cancers they were 1.7 and 2.6 respectively. The highest MR values were observed in studies of cancer cases in which MN were measured in the same tissue as the tumour (MR = 4.9–10.8).</p><p>This special issue is an important milestone in the evidence supporting MN as a reliable genomic biomarker of developmental and degenerative disease risk. These advances, together with results from prospective cohort studies, are helping to identify diseases in which MN assays can be practically employed in the clinical setting to better identify high risk patients and to prioritise them for preventive therapy.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108384"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How can exposure to engineered nanomaterials influence our epigenetic code? A review of the mechanisms and molecular targets","authors":"Luciana Moreira ,&nbsp;Carla Costa ,&nbsp;Joana Pires ,&nbsp;João Paulo Teixeira ,&nbsp;Sónia Fraga","doi":"10.1016/j.mrrev.2021.108385","DOIUrl":"10.1016/j.mrrev.2021.108385","url":null,"abstract":"<div><p>Evidence suggests that engineered nanomaterials (ENM) can induce epigenetic modifications. In this review, we provide an overview of the epigenetic modulation of gene expression induced by ENM used in a variety of applications: titanium dioxide (TiO₂), silver (Ag), gold (Au), silica (SiO₂) nanoparticles and carbon-based nanomaterials (CNM). Exposure to these ENM can trigger alterations in cell patterns of DNA methylation, post-transcriptional histone modifications and expression of non-coding RNA. Such effects are dependent on ENM dose and physicochemical properties including size, shape and surface chemistry, as well as on the cell/organism sensitivity. The genes affected are mostly involved in the regulation of the epigenetic machinery itself, as well as in apoptosis, cell cycle, DNA repair and inflammation related pathways, whose long-term alterations might lead to the onset or progression of certain pathologies. In addition, some DNA methylation patterns may be retained as a form of epigenetic memory. Prenatal exposure to ENM may impair the normal development of the offspring by transplacental effects and/or putative transmission of epimutations in imprinting genes. Thus, understanding the impact of ENM on the epigenome is of paramount importance and epigenetic evaluation must be considered when assessing the risk of ENM to human health.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108385"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39576800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic predisposition to lymphomas: Overview of rare syndromes and inherited familial variants","authors":"Bartosz Szmyd,&nbsp;Wojciech Mlynarski,&nbsp;Agata Pastorczak","doi":"10.1016/j.mrrev.2021.108386","DOIUrl":"10.1016/j.mrrev.2021.108386","url":null,"abstract":"<div><p>Approximately 10 % of malignancies occur in carriers of germline<span><span> mutations predisposing to cancer. A high risk of developing lymphomas has been noted in many primary immunodeficiencies, including DNA repair disorders. Moreover, implementation of next-generation sequencing has recently enabled to uncover rare genetic variants predisposing patients to lymphoid neoplasms. Some patients harboring inherited predisposition to lymphomas require dedicated clinical management, which will contribute to effective cancer treatment and to the prevention of potential severe toxicities and secondary malignancies. In line with that, our review summarizes the natural history of </span>lymphoid tumors developing on different germline genetic backgrounds and discusses the progress that has been made toward successfully treating these malignancies.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108386"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roadmap for translating results from the micronucleus assay into clinical practice: From observational studies to randomized controlled trials","authors":"Stefano Bonassi ,&nbsp;Michael Fenech","doi":"10.1016/j.mrrev.2021.108390","DOIUrl":"10.1016/j.mrrev.2021.108390","url":null,"abstract":"<div><p><span>According to the definition delivred by the WHO, a biomarker, independently from its role that may be indicative of exposure, response or effect, is inevitably linked to a clinical outcome or to a disease. The presence of a continuum from early biological events to therapy, and prognosis is the unifying mechanism that justifies this conclusion. Traditionally, the technical and inter-individual variability of the assays, together with the long duration between early pathogenetic events and the disease, prevented clinical applications to these biomarkers. These limitations became less important with the emerging of personalized preventive medicine because of the focus on disease prediction and prevention, and the recommended use of all data concerning measurable patient's features. Several papers have been published on the best validation procedures for translating biomarkers to real life. The history of cholesterol concentration is extensively discussed as a reliable example of a biomarker that - after a long and controversial validation process - is currently used in clinical practice. The frequency of micronucleated cells is a reliable biomarker for the pathogenesis of cancer and other non-communicable diseases, and the link with clinical outcomes is substantiated by epidemiological evidence and strong mechanistic basis. Available literature concerning the use of the </span>micronucleus assay<span> in clinical studies is discussed, and a suitable three-levels road-map driving this biomarker towards clinical practice is presented. Under the perspective of personalized medicine, the use of the micronucleus assays can play a decisive role in addressing preventive and therapeutic strategies of chronic diseases. In many cases the MN assay is either currently used in clinical practice or classified as adequate to consider translation into practice. The roadmap to clinical validation of the micronucleus assay finds inspiration from the history of biomarkers such as cholesterol, which clearly showed that the evidence from prospective studies or RCTs is critical to achieve the required level of trust from the healthcare profession. (307 words)</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108390"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}