Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"title":"Epistatic interactions in DNA repair genes as biomarkers of susceptibility for DNA damage in pesticide-exposed agricultural workers of Punjab, North-West India","authors":"Karashdeep Kaur ,&nbsp;Rupinder Kaur","doi":"10.1016/j.mrgentox.2025.503880","DOIUrl":"10.1016/j.mrgentox.2025.503880","url":null,"abstract":"<div><div>Some occupational exposures to pesticides have been associated with genotoxicity which arises from DNA single-strand breaks (SSBs), repair of DNA double-strand breaks (DSBs), DNA adduct formation, or DNA-DNA and DNA-protein cross-links. Polymorphisms in genes encoding enzymes of DNA repair pathways may modulate the individual’s susceptibility to pesticide-induced genotoxicity. A total of 450 subjects were included in this study, which comprises 225 agricultural workers exposed to complex mixtures of pesticides and 225 non-exposed controls from Punjab, North-West India. Susceptibility of <em>OGG1</em> Ser326Cys (C1245G), <em>XRCC1</em> Arg194Trp (C26304T), <em>XRCC1</em> Arg399Gln (G28152A), <em>XPC</em> Lys939Gln (A2920C), <em>XPC</em> Ala499Val (C21151T), <em>XPD</em> Asp312Asn (G23591A), <em>XPD</em> Lys715Gln (A35931C), <em>XPF</em> Arg415Gln (G1244A), <em>XPG</em> Asp1104His (G3507C), <em>ERCC1</em> 3′-UTR (C8092A) and <em>ERCC1</em> Asn118Asn (C354T) gene polymorphisms with pesticide-induced DNA damage was determined by Kruskal-Wallis test. The association of epistatic gene interactions with DNA damage was studied by ANOVA. The results indicated significant interactions of variant <em>OGG1</em> 326Ser/Cys genotype with <em>XRCC1</em> 194Arg/Trp and <em>XRCC1</em> 399Arg/Gln genotypes in increased susceptibility to DNA damage. <em>XPC</em> 939Gln/Gln genotype significantly interacts with <em>XPC</em> 499Ala/Val, <em>XPD</em> 312Asp/Asp and <em>XPD</em> 715Gln/Gln variant genotypes to increase DNA damage susceptibility. Among exposed <em>XPF</em> 415Gln/Gln individuals, DNA damage was significantly higher in those individuals who had variant <em>XPG</em> Asp/His and <em>ERCC1</em> 8092CA genotypes. We observed some statistically significant epistatic gene interactions in DNA repair pathways in modulating DNA damage, which may be used as biomarkers of susceptibility in pesticide-exposed agricultural workers of Punjab, North-West India.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503880"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773162","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":"Radiology personnel chronically exposed to low-dose ionizing radiation: Assessment of genotoxic damage with the buccal micronucleus cytome assay","authors":"Serap Yüce Emiroğlu ,&nbsp;Tülay Aşkın Çeli̇k","doi":"10.1016/j.mrgentox.2025.503872","DOIUrl":"10.1016/j.mrgentox.2025.503872","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to assess the genotoxic effects of chronic occupational exposure to low-dose ionizing radiation among healthcare professionals employed at three hospitals in Aydın, Turkey: Aydın Adnan Menderes University Research and Application Hospital (ADU-UAH), Atatürk State Hospital, and Aydın State Hospital. The exposed group comprised 27 healthcare workers routinely operating in radiation-related departments, while 27 matched individuals with no known exposure constituted the control group.</div></div><div><h3>Methods</h3><div>Genetic damage was evaluated using the exfoliated buccal micronucleus cytome (BMCyt) assay, a validated and non-invasive method for human biomonitoring. Frequencies of nuclear abnormalities—including micronuclei, binucleated cells, nuclear buds, condensed chromatin, karyorrhexis, karyolysis, and pyknotic cells—were systematically recorded and compared between groups.</div></div><div><h3>Results</h3><div>A statistically significant increase in all genotoxic markers was observed in the exposed group compared to controls (p &lt; 0.05). The highest frequency of micronucleated cells was found in workers at Aydın State Hospital (32.38 ‰), approximately 30-fold higher than the control group (2.84 ‰). Healthcare workers at ADU-UAH and Atatürk State Hospital exhibited moderate yet notable elevations, with frequencies of 24.85 ‰ and 17.28 ‰, respectively. Sex-stratified analysis revealed minor but statistically significant differences, with male workers showing slightly higher genotoxicity levels (p &lt; 0.05), although female staff exhibited higher nuclear anomalies at certain institutions.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that chronic exposure to low-dose ionizing radiation is associated with increased genomic instability among healthcare workers. The elevated frequency of nuclear abnormalities highlights a potential long-term mutagenic risk in occupational settings. These results underscore the urgent need for reinforced radiation safety protocols, routine biomonitoring, and institutional policy revisions to mitigate genotoxic risks. Further studies are warranted to elucidate the mechanisms underlying radiation-induced genomic damage and to better understand individual susceptibility patterns in exposed populations.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503872"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290487","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":"Photogenotoxicity of N-nitrosoproline plus simultaneous UVA irradiation in human-derived keratinocytes","authors":"Naomi Tomozane ,&nbsp;Noriko Tanaka ,&nbsp;Sakae Arimoto-Kobayashi","doi":"10.1016/j.mrgentox.2025.503876","DOIUrl":"10.1016/j.mrgentox.2025.503876","url":null,"abstract":"<div><div>In this study, we investigated the genotoxicity of <em>N</em>-nitrosoproline (NPRO) in human-derived keratinocytes (HaCaT and NCTC2544 cells) using simultaneous UVA irradiation without metabolic activation. NPRO plus UVA exhibited dose- and intensity-dependent micronuclei formation in the keratinocytes, as well as nitric oxide (NO) production. The action spectra of genotoxicity and NO formation from NPRO plus UVA followed the absorption curve of NPRO, indicating that photoenergy was absorbed by the NPRO-triggered photoreaction. A significant increase in cyclic guanosine monophosphate (cGMP) was observed in HaCaT cells treated with NPRO plus UVA. NO production from UVA-irradiated NPRO paralleled micronuclei formation, and the phototoxicity of NPRO may have simultaneously interfered with the cGMP-related signaling systems caused by NO from photoactivated NPRO.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503876"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631903","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":"Significant new developments in genetic toxicology testing","authors":"Miroslav Mišík,&nbsp;P. David Josephy,&nbsp;Helga Stopper,&nbsp;Siegfried Knasmueller","doi":"10.1016/j.mrgentox.2025.503873","DOIUrl":"10.1016/j.mrgentox.2025.503873","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503873"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680603","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":"Bleomycin induces short-term telomere fragility in Epstein-Barr virus-transformed human lymphoblastoid cells","authors":"Andrea G. Cardozo ,&nbsp;Daniel C. Castrogiovanni ,&nbsp;Julieta M. Parisi ,&nbsp;Alejandro D. Bolzán","doi":"10.1016/j.mrgentox.2025.503877","DOIUrl":"10.1016/j.mrgentox.2025.503877","url":null,"abstract":"<div><div>The induction of telomere dysfunction-related chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) was studied in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). To this end, an EBV-induced lymphoblastoid cell line (T-37) was exposed to increased concentrations of BLM (10–100 µg/mL) for 2 h at 37ºC, and telomere aberrations were analyzed 24 h (first mitosis) after treatment using PNA-FISH with pan-telomeric plus pan-centromeric probes. Telomere signal duplications (TSD) increased significantly in BLM-exposed cells (p &lt; 0.01), although the concentration-response relationship was non-linear. Most of the induced TSD (95–99 %) were of chromatid-type. No induction of telomere signal loss, telomere fusions or telomere associations by BLM was observed in T-37 cells. These findings show that BLM induces short-term telomere dysfunction in EBV-transformed human lymphoblastoid cells in the form of TSD (which implies telomere fragility) and suggest that these effects mainly occur during the G2 stage of the cell cycle. The persistence of this type of aberrations in the long-term in EBV-induced lymphoblastoid cells and other human cells exposed to BLM may be of medical relevance. Telomere fragility induced by BLM could promote genomic instability, which might contribute to the development of secondary tumors in patients undergoing chemotherapy based on this compound. Consequently, our study raises concerns about the potential long-term genomic effects of BLM in treated patients and suggests that the analysis of TSD could be a useful biomarker for detecting BLM-induced telomere dysfunction in human cells.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503877"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654210","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":"Genome-wide mutation analysis induced by mutagens in TK6 cells using Hawk-Seq™","authors":"Yuki Otsubo ,&nbsp;Takako Hirose ,&nbsp;Shoji Matsumura ,&nbsp;Sayaka Hosoi ,&nbsp;Kazutoshi Saito ,&nbsp;Masaaki Miyazawa","doi":"10.1016/j.mrgentox.2025.503875","DOIUrl":"10.1016/j.mrgentox.2025.503875","url":null,"abstract":"<div><div>Error-corrected next-generation sequencing (ecNGS) sensitively detects rare mutations in biological models. We applied Hawk-Seq™ to evaluate chemical-induced mutations using the IVGT TK6 human lymphoblastoid cell line. Since clonal and sub-clonal variants (CVs and SCVs) decrease mutation detection sensitivity, we first identified 4,501,430 CVs compared to GRCh38 by resequencing the TK6 genome. The overall base substitution (BS) frequency in vehicle controls after filtering out these variants was 2.0 × 10⁻⁶ base pairs (bp), relatively higher than in other ecNGS studies. A total of 4974 sites provided the same types of BSs in ≥ 2 vehicle controls, suggesting that SCVs increased the error frequency. After filtering out these sites, the overall background BS frequency significantly decreased (0.93 × 10⁻⁶ bp). Therefore, we filtered out the potential SCV positions identified using resequencing data with increased depth (mean depth of ca. 110), reducing the background overall BS frequency to 0.65 × 10⁻⁶ bp. Finally, we evaluated DNA samples from TK6 cells exposed to <em>N</em>-methyl-<em>N</em>-nitrosourea (MNU) and <em>N</em>-ethyl-<em>N</em>-nitrosourea (ENU) for 24 h. The overall BS frequencies in MNU- and ENU-treated samples were 9.0 × 10⁻⁶ and 2.0 × 10⁻⁶ bp, respectively, significantly improving the signal-to-noise ratio. MNU predominantly induced G:C &gt; A:T (21 × 10⁻⁶ bp), 62 times higher than that induced by vehicle controls. ENU primarily induced G:C &gt; A:T (2.7 × 10⁻⁶ bp) and significantly increased A:T &gt; C:G and A:T &gt; G:C frequencies (∼10⁻⁷ bp). Our method sensitively detected mutations, including minor patterns, indicating its potential to reflect various mutagenic mechanisms.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503875"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654211","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":"Low-dose bisphenol A plus arsenite: Continuous or intermittent exposures in Sprague-Dawley rats; Effects on kidney oxidative stress, DNA damage, ferroptosis, and fibrosis","authors":"Girija Prasanna Sahoo,&nbsp;Asutosh Pattnaik,&nbsp;Vinod Kumar,&nbsp;Gopabandhu Jena","doi":"10.1016/j.mrgentox.2025.503871","DOIUrl":"10.1016/j.mrgentox.2025.503871","url":null,"abstract":"<div><div>Arsenic and bisphenol A (BPA) are widespread environmental pollutants. We have studied the nephrotoxicity of arsenite (ARS), 10 mg/L in drinking water, plus BPA, 50 µg/kg oral dose, in juvenile Sprague-Dawley rats. Animals were randomized into seven groups and exposed to the chemicals either continuously or intermittently, for 8 weeks. The parameters evaluated were urine biomarkers, histopathological and transmission electron microscopic (TEM) examinations, DNA damage (halo assay), and protein expressions. Continuous exposure to AS and BPA significantly increased urinary creatinine, albumin, and total protein, and decreased blood urea nitrogen (BUN). Histopathological and TEM data showed brush border detachment, iron accumulation, podocyte injury, increased slit diaphragm space, and collagen deposition in both exposure groups. Significantly greater DNA damage was seen in the combined-exposure group than in the other experimental groups. Combination exposure in the continuous and intermittent groups showed renal fibrosis and ferroptosis and gene expression analysis revealed a significant increase in Bax and decrease in SIRT 1. Combination exposure was more harmful than the individual exposures in causing kidney injury in these animals.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503871"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887582","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":"DNA damage and oxidative stress responses to pollution of Mytilus galloprovincialis L. from the Izmir Bay (Turkey): Seasonal evaluation","authors":"Ebru Yayla ,&nbsp;Cem Guler ,&nbsp;Aylin Buhur ,&nbsp;Nefise Ulku Karabay Yavasoglu ,&nbsp;Selma Katalay ,&nbsp;Cinel Koksal Karayildirim","doi":"10.1016/j.mrgentox.2025.503866","DOIUrl":"10.1016/j.mrgentox.2025.503866","url":null,"abstract":"<div><div>In the current study, the relationship between DNA damage and heavy metal pollutions was evaluated by sampling mussels from Izmir Bay (Turkey), which has different anthropogenic impacts in the Aegean Sea. <em>M. galloprovincialis</em> was selected as a bioindicator organism to determine the heavy metal amounts, SOD, CAT, TBARS levels and to detect the DNA damage in 4 different stations of Izmir Bay. A significant increase was detected in all heavy metals in the digestive gland tissue of the mussels collected from the Alsancak in summer compared to spring. Especially, Zn levels of gills and digestive glands of mussels collected from Alsancak in summer were detected 22.411 and 40.447 μg/g, respectively. According to MPI values, significant differences were determined in Urla and the highest accumulation was calculated in gill tissue. The activities of SOD and CAT enzymes were found at a very high level in mussel gills and glands at all stations except Urla in summer compared to them in spring. Additionally, TBARS levels were higher in mussel gills and gonad tissues at Inciralti and Urla stations in summer compared to spring samples. DNA damage classification in mussel hemocytes from all stations was identified according to the Comet assay. The test results showed that a statistically significant decrease in DNA% in comet tails in hemocytes of mussels collected from all stations in Summer was found compared to them in Spring. Also, at all stations except Alsancak, the genetic damage index decreased in summer compared to spring. While a positive correlation was detected between heavy metal pollution and DNA damage in mussels taken from Alsancak and Inciraltı (r = 0.734), a significant correlation was detected in Pasaport and Urla in both seasons (r = 0.999). This study indicates that heavy metal contaminations in the mussels of Izmir Bay are still an environmental problem on this area. DNA damage is an appropriate biomarker for genotoxicity evaluation even in low heavy metal contaminated areas.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503866"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768375","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 study of radiation workers: Dosimetry, chromosomal aberrations, and cancer risk","authors":"Gyöngyi Farkas ,&nbsp;Réka Király ,&nbsp;Gábor Székely ,&nbsp;Zsuzsa S. Kocsis ,&nbsp;Gyöngyvér Orsolya Sándor ,&nbsp;Csilla Pesznyák ,&nbsp;Tibor Major ,&nbsp;Zoltán-Takácsi Nagy ,&nbsp;Zsolt Jurányi","doi":"10.1016/j.mrgentox.2025.503869","DOIUrl":"10.1016/j.mrgentox.2025.503869","url":null,"abstract":"<div><div>Cytogenetic analysis of blood lymphocytes can be used as a biomarker of absorbed radiation dose. The frequency of chromosomal aberrations (CA) correlates with subsequent cancer incidence. Healthy medical employees in Hungary - 301 working in an ionizing radiation work area and 732 controls - were studied from 1997 to 2022. Frequencies of chromatid- and chromosome-type aberrations in peripheral blood lymphocytes were significantly higher in the ionizing radiation group. Smoking also affected the frequency of aberrations, which was highest among smokers in the radiation group. Staff working with ionizing radiation were divided into four groups: CT, radiation therapy, diagnostic X-ray, and nuclear medicine. Total aberrations and aberrant cells were significantly higher in the nuclear medicine group than in the CT group. Tumor cases were not more frequent among the ionizing radiation group than among the control group.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503869"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834251","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":"New Approach Methods (NAMs) for genotoxicity assessment of nano- and advanced materials; Advantages and challenges","authors":"Arno C. Gutleb ,&nbsp;Sivakumar Murugadoss ,&nbsp;Maciej Stępnik ,&nbsp;Tanima SenGupta ,&nbsp;Naouale El Yamani ,&nbsp;Eleonora Marta Longhin ,&nbsp;Ann-Karin Hardie Olsen ,&nbsp;Ewelina Wyrzykowska ,&nbsp;Karolina Jagiello ,&nbsp;Beata Judzinska ,&nbsp;Sebastien Cambier ,&nbsp;Tatiana Honza ,&nbsp;Erin McFadden ,&nbsp;Sergey Shaposhnikov ,&nbsp;Tomasz Puzyn ,&nbsp;Tommaso Serchi ,&nbsp;Pamina Weber ,&nbsp;Emma Arnesdotter ,&nbsp;Vier Skakalova ,&nbsp;Katerina Jirsova ,&nbsp;Maria Dusinska","doi":"10.1016/j.mrgentox.2025.503867","DOIUrl":"10.1016/j.mrgentox.2025.503867","url":null,"abstract":"<div><div>Genotoxicity assessment is essential for ensuring chemical safety and mitigating risks to human health and the environment. Traditional methods, reliant on animal models, are time-consuming, costly, and raise ethical concerns. New Approach Methods (NAMs) offer innovative, cost-effective, and ethical alternatives, playing a pivotal role in both traditional and next-generation risk assessment (NGRA) by minimizing the need for animal testing, particularly in genotoxicity evaluations. However, the development of NAMs often overlooks the particular physicochemical properties of nanomaterials (NMs), which significantly influence their toxicological behaviour and can interfere with genotoxicity evaluation. This underscores an urgent need for the standardization and adaptation of NAMs to address nano- and advanced material-specific genotoxicity challenges. In this review, we summarize the challenges associated with genotoxicity testing of NMs and highlight the suitability of existing <em>in vitro</em> and <em>in silico</em> NAMs for NMs and advanced materials, enabling genotoxicity testing across various exposure routes and organ systems. Despite considerable progress, regulatory validation remains constrained by the absence of approved test guidelines and standardized protocols. To achieve regulatory acceptance, it is crucial to adapt NAMs to NM-specific exposure scenarios, refine test systems to better mimic human biology, develop tailored <em>in vitro</em> protocols, and ensure thorough characterisation of NMs both in pristine form and dispersed in culture medium. Collaborative efforts among scientists, regulators, industry, and advocacy groups are vital to improving the reliability and regulatory acceptance of NAMs. By addressing these challenges, NAMs have the potential to revolutionize genotoxicity risk assessment, advancing it towards a more sustainable, efficient and ethical framework.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503867"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768376","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}