Pub Date : 2026-02-02DOI: 10.1016/j.mrrev.2026.108585
Monika Rajput, Manoj Pandey
Natural background radiation (NBR) delivers chronic low-dose-rate ionizing radiation worldwide, with a global average annual effective dose of ∼2.4 mSv. In certain high-background radiation areas (HBRAs), annual doses range from 10 to > 200 mSv. While the linear no-threshold (LNT) model assumes any radiation dose carries some cancer risk, epidemiological studies in HBRAs (Kerala-India, Ramsar-Iran, Yangjiang-China, Guarapari-Brazil) have consistently failed to detect the predicted cancer excess. Some cytogenetic and molecular investigations suggest enhanced DNA repair proficiency or lower-than-expected chromosomal damage in chronically exposed residents. This narrative review critically synthesizes epidemiological, cytogenetic, and limited molecular evidence from HBRAs, evaluates the ability of current dose-response models (LNT versus non-linear alternatives) to explain these observations, identifies major knowledge gaps, and discusses implications for low-dose radiation risk assessment and public health policy.
{"title":"Biological effects and potential genetic/epigenetic adaptive responses to chronic natural background radiation.","authors":"Monika Rajput, Manoj Pandey","doi":"10.1016/j.mrrev.2026.108585","DOIUrl":"https://doi.org/10.1016/j.mrrev.2026.108585","url":null,"abstract":"<p><p>Natural background radiation (NBR) delivers chronic low-dose-rate ionizing radiation worldwide, with a global average annual effective dose of ∼2.4 mSv. In certain high-background radiation areas (HBRAs), annual doses range from 10 to > 200 mSv. While the linear no-threshold (LNT) model assumes any radiation dose carries some cancer risk, epidemiological studies in HBRAs (Kerala-India, Ramsar-Iran, Yangjiang-China, Guarapari-Brazil) have consistently failed to detect the predicted cancer excess. Some cytogenetic and molecular investigations suggest enhanced DNA repair proficiency or lower-than-expected chromosomal damage in chronically exposed residents. This narrative review critically synthesizes epidemiological, cytogenetic, and limited molecular evidence from HBRAs, evaluates the ability of current dose-response models (LNT versus non-linear alternatives) to explain these observations, identifies major knowledge gaps, and discusses implications for low-dose radiation risk assessment and public health policy.</p>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"108585"},"PeriodicalIF":4.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114717","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}
Pub Date : 2026-01-01DOI: 10.1016/j.mrrev.2025.108583
Peter Møller , Goran Gajski , Marko Gerić , Anja Haveric , Helga Stopper , Ezgi Eyluel Bankoglu , Amaya Azqueta , Lisa Giovannelli , Andrew Collins , Carina Ladeira
Humans are exposed to environmental or occupational air pollution from combustion emissions in outdoor and indoor environments. Irrespective of the sources, combustion emissions are characterized by being a complex mixture of particles, volatile compounds and gases. The present systematic review summarizes results on DNA strand breaks measured by the comet assay in leukocytes, from studies on human exposure to traffic-related vehicle exhaust, biomass combustion and coke oven work environments. These exposures have in common the combustion of fuel, which generates particles and polycyclic aromatic hydrocarbons. Standardized mean differences (SMDs) have been calculated by random effects models. Meta-analyses show increased levels of DNA strand breaks in studies on traffic-related exhausts (SMD = 0.62, 95 % CI: 0.36, 0.89, n = 21), biomass combustion (1.73, 95 % CI: 0.72, 2.74, n = 10) and coke oven emission (0.84, 95 % CI: 0.30, 1.37, n = 10). Studies from high-income countries have reported much smaller differences in DNA strand break levels than have studies from middle-income countries. These differences may be attributed to higher exposures related to less strict emission control, and more susceptible populations in middle-income populations; unrecognized confounding despite efforts to match subjects on traditional confounders; or higher risk of comet assay measurement bias and exposure misclassification. In conclusion, this systematic review and meta-analysis show that exposure to combustion-derived air pollution, with clear exposure gradients in terms of particulate matter or polycyclic aromatic hydrocarbons, is associated with increased levels of DNA strand breaks in human leukocytes.
人类暴露于室外和室内环境中燃烧排放的环境或职业空气污染。无论其来源如何，燃烧排放物的特点是微粒、挥发性化合物和气体的复杂混合物。本系统综述总结了人类暴露于交通相关车辆尾气、生物质燃烧和焦炉工作环境中白细胞DNA链断裂的彗星测定结果。这些暴露的共同点是燃料燃烧，产生颗粒和多环芳烃。标准化平均差（SMDs）已通过随机效应模型计算。荟萃分析显示，在交通相关排放（SMD = 0.62, 95% CI: 0.36, 0.89, n = 21）、生物质燃烧（1.73,95% CI: 0.72, 2.74, n = 10）和焦炉排放（0.84,95% CI: 0.30, 1.37, n = 10）的研究中，DNA链断裂水平有所增加。来自高收入国家的研究报告显示，DNA链断裂水平的差异比来自中等收入国家的研究报告要小得多。这些差异可能归因于与排放控制不严格相关的较高暴露，以及中等收入人群中更容易受到影响；尽管在传统混杂因素上努力匹配受试者，但未被识别的混杂；或者彗星试验测量偏倚和暴露错误分类的风险更高。总之，本系统综述和荟萃分析表明，暴露于燃烧产生的空气污染，在颗粒物或多环芳烃方面具有明显的暴露梯度，与人类白细胞中DNA链断裂水平增加有关。
{"title":"The comet assay as a tool in human biomonitoring exposure to combustion-derived air pollution − A systematic review and meta-analysis","authors":"Peter Møller , Goran Gajski , Marko Gerić , Anja Haveric , Helga Stopper , Ezgi Eyluel Bankoglu , Amaya Azqueta , Lisa Giovannelli , Andrew Collins , Carina Ladeira","doi":"10.1016/j.mrrev.2025.108583","DOIUrl":"10.1016/j.mrrev.2025.108583","url":null,"abstract":"<div><div>Humans are exposed to environmental or occupational air pollution from combustion emissions in outdoor and indoor environments. Irrespective of the sources, combustion emissions are characterized by being a complex mixture of particles, volatile compounds and gases. The present systematic review summarizes results on DNA strand breaks measured by the comet assay in leukocytes, from studies on human exposure to traffic-related vehicle exhaust, biomass combustion and coke oven work environments. These exposures have in common the combustion of fuel, which generates particles and polycyclic aromatic hydrocarbons. Standardized mean differences (SMDs) have been calculated by random effects models. Meta-analyses show increased levels of DNA strand breaks in studies on traffic-related exhausts (SMD = 0.62, 95 % CI: 0.36, 0.89, n = 21), biomass combustion (1.73, 95 % CI: 0.72, 2.74, n = 10) and coke oven emission (0.84, 95 % CI: 0.30, 1.37, n = 10). Studies from high-income countries have reported much smaller differences in DNA strand break levels than have studies from middle-income countries. These differences may be attributed to higher exposures related to less strict emission control, and more susceptible populations in middle-income populations; unrecognized confounding despite efforts to match subjects on traditional confounders; or higher risk of comet assay measurement bias and exposure misclassification. In conclusion, this systematic review and meta-analysis show that exposure to combustion-derived air pollution, with clear exposure gradients in terms of particulate matter or polycyclic aromatic hydrocarbons, is associated with increased levels of DNA strand breaks in human leukocytes.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108583"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900527","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}
There is a growing body of epidemiological evidence for elevated risks of a variety of multifactorial diseases such as cancer, neurodegenerative diseases (e.g., Parkinson’s disease and dementia) and cerebrovascular diseases (e.g., stroke) following radiation exposure of the brain. Implications of available scientific evidence for radiation protection need to be assessed, e.g., in terms of radiation effect classification (tissue reactions vs stochastic effects), dose and dose-rate effectiveness, target identification (at levels of cells, tissues and organs inside/outside the brain) for dose monitoring and risk management, radiation weighting approach for the mixed radiation field, and individual differences in radiation responses (e.g., with sex, age, populations, genetics, epigenetics, comorbidity, co-exposure). On the other hand, whole brain irradiation has clinically been tested to treat neurodegenerative diseases, particularly Alzheimer’s disease. Action of radiation seems to represent a double-edged sword (i.e., detrimental to the healthy brain vs therapeutic to the diseased brain) not only for cancer, but also for non-cancer diseases. Justification of radiation exposure and optimization of radiation protection would therefore be of critical importance. This paper gives a brief overview of emerging evidence for radiation effects in the brain, and considers its potential implications for radiation protection.
{"title":"Health effects of ionizing radiation exposure in the brain: MELODI perspectives on potential implications of emerging evidence for radiation protection","authors":"Nobuyuki Hamada , Marie-Odile Bernier , Katalin Lumniczky , Dominique Laurier","doi":"10.1016/j.mrrev.2025.108582","DOIUrl":"10.1016/j.mrrev.2025.108582","url":null,"abstract":"<div><div>There is a growing body of epidemiological evidence for elevated risks of a variety of multifactorial diseases such as cancer, neurodegenerative diseases (e.g., Parkinson’s disease and dementia) and cerebrovascular diseases (e.g., stroke) following radiation exposure of the brain. Implications of available scientific evidence for radiation protection need to be assessed, e.g., in terms of radiation effect classification (tissue reactions vs stochastic effects), dose and dose-rate effectiveness, target identification (at levels of cells, tissues and organs inside/outside the brain) for dose monitoring and risk management, radiation weighting approach for the mixed radiation field, and individual differences in radiation responses (e.g., with sex, age, populations, genetics, epigenetics, comorbidity, co-exposure). On the other hand, whole brain irradiation has clinically been tested to treat neurodegenerative diseases, particularly Alzheimer’s disease. Action of radiation seems to represent a double-edged sword (i.e., detrimental to the healthy brain vs therapeutic to the diseased brain) not only for cancer, but also for non-cancer diseases. Justification of radiation exposure and optimization of radiation protection would therefore be of critical importance. This paper gives a brief overview of emerging evidence for radiation effects in the brain, and considers its potential implications for radiation protection.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108582"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884712","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}
Pub Date : 2026-01-01DOI: 10.1016/j.mrrev.2025.108584
Lisa Giovannelli , Peter Møller , Goran Gajski , Helga Stopper , Amaya Azqueta , Ezgi Eyluel Bankoglu , Anja Haveric , Marko Gerić , Andrew Collins , Carina Ladeira
Exposure to volatile organic compounds (VOCs) such as benzene, styrene, toluene and formaldehyde is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed the effects of VOCs exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. The literature search led to 57 studies included in the review. Of these, 50 studies met the criteria to be used in the meta-analysis. Using standardized mean difference and 95 % confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to benzene (1.59, 95 % CI: 0.94, 2.24), styrene (0.87, 95 % CI: 0.23, 1.51), formaldehyde (0.39, 95 % CI: −0.15, 0.92) and other organic solvents (2.14, 95 % CI: 1.48, 2.81). Results originate mainly from studies on workers, with only a few studies on environmental benzene exposure. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.81, 95 % CI: 1.26, 2.36, n = 28) than studies from high-income countries (0.87, 95 % CI: 0.49, 1.24, n = 22). This difference between middle- and high-income countries may be due to differences in exposure levels or exposure assessment. However, this might not be the only reason, as sensitivity analysis indicates that effect sizes are at risk of comet assay measurement bias, as 78 % (39 out of 50 studies) and 60 % (30 studies) have not reported the use of assay controls and blinded analysis of samples, respectively. Relatively few studies have a high risk of bias due to an inadequate comet assay procedure description (14 %, 7 studies) and exposure misclassification (16 %, 8 studies). Limitations of the study were the differences in protocols, comet descriptors, exposure assessment and control for confounding factors among the studies. In conclusion, this systematic review and meta-analysis shows that exposure to VOCs – benzene, styrene, formaldehyde and others – is associated with increased levels of DNA strand breaks in human leukocytes.
{"title":"The comet assay as a tool in human biomonitoring exposure to volatile organic compounds – A systematic review and meta-analysis","authors":"Lisa Giovannelli , Peter Møller , Goran Gajski , Helga Stopper , Amaya Azqueta , Ezgi Eyluel Bankoglu , Anja Haveric , Marko Gerić , Andrew Collins , Carina Ladeira","doi":"10.1016/j.mrrev.2025.108584","DOIUrl":"10.1016/j.mrrev.2025.108584","url":null,"abstract":"<div><div>Exposure to volatile organic compounds (VOCs) such as benzene, styrene, toluene and formaldehyde is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed the effects of VOCs exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. The literature search led to 57 studies included in the review. Of these, 50 studies met the criteria to be used in the meta-analysis. Using standardized mean difference and 95 % confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to benzene (1.59, 95 % CI: 0.94, 2.24), styrene (0.87, 95 % CI: 0.23, 1.51), formaldehyde (0.39, 95 % CI: −0.15, 0.92) and other organic solvents (2.14, 95 % CI: 1.48, 2.81). Results originate mainly from studies on workers, with only a few studies on environmental benzene exposure. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.81, 95 % CI: 1.26, 2.36, n = 28) than studies from high-income countries (0.87, 95 % CI: 0.49, 1.24, n = 22). This difference between middle- and high-income countries may be due to differences in exposure levels or exposure assessment. However, this might not be the only reason, as sensitivity analysis indicates that effect sizes are at risk of comet assay measurement bias, as 78 % (39 out of 50 studies) and 60 % (30 studies) have not reported the use of assay controls and blinded analysis of samples, respectively. Relatively few studies have a high risk of bias due to an inadequate comet assay procedure description (14 %, 7 studies) and exposure misclassification (16 %, 8 studies). Limitations of the study were the differences in protocols, comet descriptors, exposure assessment and control for confounding factors among the studies. In conclusion, this systematic review and meta-analysis shows that exposure to VOCs – benzene, styrene, formaldehyde and others – is associated with increased levels of DNA strand breaks in human leukocytes.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108584"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900967","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}
Oral cancer poses a significant health challenge in Southeast Asia, with a high incidence and mortality. Despite extensive genomic research, a molecular classification for this disease is lacking. This study aimed to address this gap by proposing a molecular classification of oral cancer based on genetic alterations. We conducted a comprehensive literature search on PubMed, identifying 8176 articles related to oral cancer genomics. From these, we selected studies focusing on genomics and compiled a list of 48 genes implicated in carcinogenesis, cross-referencing our findings with the TCGA database. Using cluster analysis and gene ontology, we grouped these genes by function and interactions, and then constructed protein-protein interaction networks to develop our proposed classification. Our results categorize the genes into five main groups: cell-cycle dysregulation (including growth activation and apoptotic dysregulation), immune-mediated, xenobiotic metabolism-associated, inflammatory pathway activation, and viral protein activation. Cell-cycle dysregulation was the most frequently studied, affecting over 60 % of cases, with TP53 being the most common alteration. While immune-mediated and inflammatory pathways are recognized for their therapeutic relevance, xenobiotic and viral mechanisms remain less explored. This review provides the first molecular classification of oral cancer, identifying five key carcinogenic pathways. This framework is expected to improve our understanding of the molecular diversity of oral cancer and guide the development of targeted therapies, especially for understudied pathways like xenobiotic metabolism and inflammation.
{"title":"Unveiling oral cancer’s molecular blueprint: A novel classification to guide precision therapy","authors":"Manoj Pandey , Pooja Singh , Mridula Shukla , Monika Rajput , Ruhi Dixit","doi":"10.1016/j.mrrev.2025.108580","DOIUrl":"10.1016/j.mrrev.2025.108580","url":null,"abstract":"<div><div>Oral cancer poses a significant health challenge in Southeast Asia, with a high incidence and mortality. Despite extensive genomic research, a molecular classification for this disease is lacking. This study aimed to address this gap by proposing a molecular classification of oral cancer based on genetic alterations. We conducted a comprehensive literature search on PubMed, identifying 8176 articles related to oral cancer genomics. From these, we selected studies focusing on genomics and compiled a list of 48 genes implicated in carcinogenesis, cross-referencing our findings with the TCGA database. Using cluster analysis and gene ontology, we grouped these genes by function and interactions, and then constructed protein-protein interaction networks to develop our proposed classification. Our results categorize the genes into five main groups: cell-cycle dysregulation (including growth activation and apoptotic dysregulation), immune-mediated, xenobiotic metabolism-associated, inflammatory pathway activation, and viral protein activation. Cell-cycle dysregulation was the most frequently studied, affecting over 60 % of cases, with TP53 being the most common alteration. While immune-mediated and inflammatory pathways are recognized for their therapeutic relevance, xenobiotic and viral mechanisms remain less explored. This review provides the first molecular classification of oral cancer, identifying five key carcinogenic pathways. This framework is expected to improve our understanding of the molecular diversity of oral cancer and guide the development of targeted therapies, especially for understudied pathways like xenobiotic metabolism and inflammation.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108580"},"PeriodicalIF":4.2,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840815","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}
Pub Date : 2025-12-20DOI: 10.1016/j.mrrev.2025.108581
Stanislav Kyzek , Sára Pišteková , Ivana Kyzeková , Mária Peťková , Veronika Medvecká , Jana Makuková , Terézia Zajičková , Samantha Hughes , Eliška Gálová , Andrea Ševčovičová
Non-thermal plasma (NTP), a partially ionized gas enriched with reactive oxygen and nitrogen species (RONS) and UV radiation, is increasingly used in medicine, agriculture, and food processing applications. While its oxidative and antimicrobial effects are well documented, the molecular mechanisms underlying its genotoxic and mutagenic effects in eukaryotic systems remain poorly understood. This review consolidates the current evidence on how NTP interacts with cellular and molecular targets to induce DNA damage. Key mechanisms are identified that link plasma-generated RONS and physical components to base oxidation (8-oxoG formation), single- and double-strand breaks (γ-H2AX foci), and chromosomal instability (micronuclei formation). The extent and nature of these effects are further influenced by plasma parameters—including source configuration, working gas composition, exposure duration, and delivered dose—as well as by intrinsic cellular factors such as DNA repair capacity, antioxidant defenses, and overall metabolic state. In addition to cataloguing genotoxic outcomes, this review synthesizes mechanistic insights across unicellular, plant, and animal models, emphasizing comparative sensitivity, methodological variability, and the influence of plasma dosimetry on biological responses. By integrating these findings, we highlight both the potential therapeutic selectivity of NTP—particularly against tumor cells—and the remaining challenges for safe biomedical translation.
{"title":"Genotoxic and mutagenic potential of non-thermal plasma: Mechanistic insights from eukaryotic cell studies","authors":"Stanislav Kyzek , Sára Pišteková , Ivana Kyzeková , Mária Peťková , Veronika Medvecká , Jana Makuková , Terézia Zajičková , Samantha Hughes , Eliška Gálová , Andrea Ševčovičová","doi":"10.1016/j.mrrev.2025.108581","DOIUrl":"10.1016/j.mrrev.2025.108581","url":null,"abstract":"<div><div>Non-thermal plasma (NTP), a partially ionized gas enriched with reactive oxygen and nitrogen species (RONS) and UV radiation, is increasingly used in medicine, agriculture, and food processing applications. While its oxidative and antimicrobial effects are well documented, the molecular mechanisms underlying its genotoxic and mutagenic effects in eukaryotic systems remain poorly understood. This review consolidates the current evidence on how NTP interacts with cellular and molecular targets to induce DNA damage. Key mechanisms are identified that link plasma-generated RONS and physical components to base oxidation (8-oxoG formation), single- and double-strand breaks (γ-H2AX foci), and chromosomal instability (micronuclei formation). The extent and nature of these effects are further influenced by plasma parameters—including source configuration, working gas composition, exposure duration, and delivered dose—as well as by intrinsic cellular factors such as DNA repair capacity, antioxidant defenses, and overall metabolic state. In addition to cataloguing genotoxic outcomes, this review synthesizes mechanistic insights across unicellular, plant, and animal models, emphasizing comparative sensitivity, methodological variability, and the influence of plasma dosimetry on biological responses. By integrating these findings, we highlight both the potential therapeutic selectivity of NTP—particularly against tumor cells—and the remaining challenges for safe biomedical translation.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108581"},"PeriodicalIF":4.2,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811922","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}
Peroxisomes are essential, highly conserved organelles in eukaryotic cells, with well-characterized roles in fatty acid β-oxidation, ether phospholipid (a key component of myelin lipid) synthesis, and maintaining redox homeostasis. Peroxisomal disorders primarily arise from abnormalities in peroxisome biogenesis or degradation, as well as enzyme deficiencies, often with genetic mutations serving as their underlying drivers. To date, effective therapeutic strategies for these disorders remain scarce. This review focuses on elucidating the pathogenesis of peroxisome biogenesis disorders (PBDs), while also clarifying the diagnostic and therapeutic approaches for PBDs specifically. It also includes a brief discussion on the role of artificial intelligence (AI) in the management of these disorders. This ultimately aims to provide a theoretical basis and practical reference for future clinical interventions.
{"title":"Elucidation of the pathogenesis of peroxisome biogenesis disorders (PBDs): From molecular mechanisms to diagnosis-therapy linkages and AI-assisted potential","authors":"Rongke Xiang, Minggao Jiang, Hanrui Xu, Ying-Qiang Shen","doi":"10.1016/j.mrrev.2025.108579","DOIUrl":"10.1016/j.mrrev.2025.108579","url":null,"abstract":"<div><div>Peroxisomes are essential, highly conserved organelles in eukaryotic cells, with well-characterized roles in fatty acid β-oxidation, ether phospholipid (a key component of myelin lipid) synthesis, and maintaining redox homeostasis. Peroxisomal disorders primarily arise from abnormalities in peroxisome biogenesis or degradation, as well as enzyme deficiencies, often with genetic mutations serving as their underlying drivers. To date, effective therapeutic strategies for these disorders remain scarce. This review focuses on elucidating the pathogenesis of peroxisome biogenesis disorders (PBDs), while also clarifying the diagnostic and therapeutic approaches for PBDs specifically. It also includes a brief discussion on the role of artificial intelligence (AI) in the management of these disorders. This ultimately aims to provide a theoretical basis and practical reference for future clinical interventions.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108579"},"PeriodicalIF":4.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783446","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}
Pub Date : 2025-12-08DOI: 10.1016/j.mrrev.2025.108578
Jianjian Zhuang , Yue Li , Yingqiong Zhang , Yiling Huang , Yijia Han , Nengming Lin , Yangling Li
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, and its incidence increases with age and is more common in elderly population. The current treatment methods for AML mainly include chemotherapy, targeted therapy, immunotherapy and hematopoietic stem cell transplantation, among which chemotherapy and targeted therapy are the most common methods. Combined therapy further enhances the therapeutic effect of AML and reduces drug toxicity. At present, drug resistance is a common problem in the treatment of AML. Gene mutations and treatment-induced mutations are the main causes of drug resistance in AML, and drug resistance is also generated during the interaction between tumor microenvironment and AML. Real-time monitoring of tumor markers such as the most common gene mutations and the changes of novel biomarkers, provides certain reference value for the occurrence of AML and the prevention of drug resistance in the process of AML diagnosis and treatment. Finally, a new direction in the future diagnosis and treatment of AML is proposed based on the current diagnosis and treatment status.
{"title":"Mechanisms, treatment strategies and predictive biomarkers of drug resistance in acute myeloid leukemia","authors":"Jianjian Zhuang , Yue Li , Yingqiong Zhang , Yiling Huang , Yijia Han , Nengming Lin , Yangling Li","doi":"10.1016/j.mrrev.2025.108578","DOIUrl":"10.1016/j.mrrev.2025.108578","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, and its incidence increases with age and is more common in elderly population. The current treatment methods for AML mainly include chemotherapy, targeted therapy, immunotherapy and hematopoietic stem cell transplantation, among which chemotherapy and targeted therapy are the most common methods. Combined therapy further enhances the therapeutic effect of AML and reduces drug toxicity. At present, drug resistance is a common problem in the treatment of AML. Gene mutations and treatment-induced mutations are the main causes of drug resistance in AML, and drug resistance is also generated during the interaction between tumor microenvironment and AML. Real-time monitoring of tumor markers such as the most common gene mutations and the changes of novel biomarkers, provides certain reference value for the occurrence of AML and the prevention of drug resistance in the process of AML diagnosis and treatment. Finally, a new direction in the future diagnosis and treatment of AML is proposed based on the current diagnosis and treatment status.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108578"},"PeriodicalIF":4.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726920","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}
Pub Date : 2025-12-05DOI: 10.1016/j.mrrev.2025.108577
Alannah J. DiCintio, Alan S. Waldman
The maintenance of the genome in eukaryotic cells is dependent on the proper maintenance of the structure and function of the nuclear envelope which encases the genome. The nuclear envelope in higher eukaryotic cells is composed of the outer nuclear membrane, the inner nuclear membrane, and the nuclear lamina which resides just inside of the inner nuclear membrane. The nuclear lamina provides mechanical support to the nuclear envelope, plays essential roles in transport of molecules between the cytoplasm and the nucleus, and is pivotal in regulating global chromatin structure and three-dimensional nuclear architecture. Proper functioning of the nuclear lamina plays roles in regulating the cell cycle, transcription, RNA splicing, chromatin organization, DNA replication, and DNA repair. The nuclear lamina is conserved in metazoans and is composed of a meshwork of interwoven proteins called lamins, as well as lamin associated proteins. The protein known as lamin A is a vital constituent of the nuclear lamina. Alterations in lamin A, particularly those associated with disruptions in posttranslational processing of lamin A by zinc metallopeptidase ste24, have been linked to a variety of genetic disorders that give rise to genome instability and accelerated aging. This review will concentrate primarily on what has been learned about the dependency of effective DNA repair and DNA replication on a functional nuclear lamina, with particular emphasis on how modifications in the protein lamin A may corrupt a cell’s ability to maintain genome stability.
{"title":"The impact of alterations in lamin A on genome integrity","authors":"Alannah J. DiCintio, Alan S. Waldman","doi":"10.1016/j.mrrev.2025.108577","DOIUrl":"10.1016/j.mrrev.2025.108577","url":null,"abstract":"<div><div>The maintenance of the genome in eukaryotic cells is dependent on the proper maintenance of the structure and function of the nuclear envelope which encases the genome. The nuclear envelope in higher eukaryotic cells is composed of the outer nuclear membrane, the inner nuclear membrane, and the nuclear lamina which resides just inside of the inner nuclear membrane. The nuclear lamina provides mechanical support to the nuclear envelope, plays essential roles in transport of molecules between the cytoplasm and the nucleus, and is pivotal in regulating global chromatin structure and three-dimensional nuclear architecture. Proper functioning of the nuclear lamina plays roles in regulating the cell cycle, transcription, RNA splicing, chromatin organization, DNA replication, and DNA repair. The nuclear lamina is conserved in metazoans and is composed of a meshwork of interwoven proteins called lamins, as well as lamin associated proteins. The protein known as lamin A is a vital constituent of the nuclear lamina. Alterations in lamin A, particularly those associated with disruptions in posttranslational processing of lamin A by zinc metallopeptidase ste24, have been linked to a variety of genetic disorders that give rise to genome instability and accelerated aging. This review will concentrate primarily on what has been learned about the dependency of effective DNA repair and DNA replication on a functional nuclear lamina, with particular emphasis on how modifications in the protein lamin A may corrupt a cell’s ability to maintain genome stability.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"797 ","pages":"Article 108577"},"PeriodicalIF":4.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685863","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}
Pub Date : 2025-07-01DOI: 10.1016/j.mrrev.2025.108559
Gisella Figlioli , Amandine Billaud , Paolo Peterlongo
The FANCM gene is involved in the Fanconi Anemia (FA) DNA repair pathway. Although germline biallelic pathogenic variants in genes of this pathway cause the recessive FA syndrome, the role of FANCM in FA or FA-like has been questioned. Biallelic FANCM protein truncating variants (PTVs) have been primarily linked to infertility and cancer, suggesting the gene causes a clinically distinct phenotype. Four literature databases were systematically searched from inception to June 2024 to identify published articles describing individuals carrying biallelic PTVs in FANCM. Twenty articles describing 40 carriers of biallelic FANCM PTVs were identified. We established genotype-phenotype correlations and found that women carrying biallelic combinations of the C-terminal p.Gln1701* and p.Gly1906Alafs*12 PTVs showed infertility, chromosome fragility, breast cancer, and chemotoxicity. Men carrying the same PTVs combinations showed infertility only. Carriers of biallelic combinations including a single N-terminal PTV showed chromosome fragility, infertility, and early onset breast cancer and/or squamous cell carcinoma, and pediatric hematological cancers, often associated with severe chemotoxicity. Our findings indicate that FANCM biallelic PTVs may cause a novel recessive syndrome which is distinct from FA and characterized by infertility, chromosome fragility, cancer and chemotoxicity. While infertility is always observed, the severity of chromosome fragility, cancer predisposition and chemotoxicity seem to depend on FANCM PTVs position and the sex of the carrier. Larger analyses are warranted to consolidate these findings.
{"title":"Genotype-phenotype correlations in biallelic carriers of FANCM protein truncating variants: A systematic literature review","authors":"Gisella Figlioli , Amandine Billaud , Paolo Peterlongo","doi":"10.1016/j.mrrev.2025.108559","DOIUrl":"10.1016/j.mrrev.2025.108559","url":null,"abstract":"<div><div>The <em>FANCM</em> gene is involved in the Fanconi Anemia (FA) DNA repair pathway. Although germline biallelic pathogenic variants in genes of this pathway cause the recessive FA syndrome, the role of <em>FANCM</em> in FA or FA-like has been questioned. Biallelic <em>FANCM</em> protein truncating variants (PTVs) have been primarily linked to infertility and cancer, suggesting the gene causes a clinically distinct phenotype. Four literature databases were systematically searched from inception to June 2024 to identify published articles describing individuals carrying biallelic PTVs in <em>FANCM</em>. Twenty articles describing 40 carriers of biallelic <em>FANCM</em> PTVs were identified. We established genotype-phenotype correlations and found that women carrying biallelic combinations of the C-terminal p.Gln1701* and p.Gly1906Alafs*12 PTVs showed infertility, chromosome fragility, breast cancer, and chemotoxicity. Men carrying the same PTVs combinations showed infertility only. Carriers of biallelic combinations including a single N-terminal PTV showed chromosome fragility, infertility, and early onset breast cancer and/or squamous cell carcinoma, and pediatric hematological cancers, often associated with severe chemotoxicity. Our findings indicate that <em>FANCM</em> biallelic PTVs may cause a novel recessive syndrome which is distinct from FA and characterized by infertility, chromosome fragility, cancer and chemotoxicity. While infertility is always observed, the severity of chromosome fragility, cancer predisposition and chemotoxicity seem to depend on <em>FANCM</em> PTVs position and the sex of the carrier. Larger analyses are warranted to consolidate these findings.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108559"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852994","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}
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