Mutagenesis最新文献

{"title":"Visual comet scoring revisited: a guide to scoring comet assay slides and obtaining reliable results.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Julen Sanz-Serrano,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo,&nbsp;Patrizia Riso,&nbsp;Congying Zheng,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead015","DOIUrl":"10.1093/mutage/gead015","url":null,"abstract":"<p><p>Measurement of DNA migration in the comet assay can be done by image analysis or visual scoring. The latter accounts for 20%-25% of the published comet assay results. Here we assess the intra- and inter-investigator variability in visual scoring of comets. We include three training sets of comet images, which can be used as reference for researchers who wish to use visual scoring of comets. Investigators in 11 different laboratories scored the comet images using a five-class scoring system. There is inter-investigator variation in the three training sets of comets (i.e. coefficient of variation (CV) = 9.7%, 19.8%, and 15.2% in training sets I-III, respectively). However, there is also a positive correlation of inter-investigator scoring in the three training sets (r = 0.60). Overall, 36% of the variation is attributed to inter-investigator variation and 64% stems from intra-investigator variation in scoring between comets (i.e. the comets in training sets I-III look slightly different and this gives rise to heterogeneity in scoring). Intra-investigator variation in scoring was also assessed by repeated analysis of the training sets by the same investigator. There was larger variation when the training sets were scored over a period of six months (CV = 5.9%-9.6%) as compared to 1 week (CV = 1.3%-6.1%). A subsequent study revealed a high inter-investigator variation when premade slides, prepared in a central laboratory, were stained and scored by investigators in different laboratories (CV = 105% and 18%-20% in premade slides with comets from unexposed and hydrogen peroxide-exposed cells, respectively). The results indicate that further standardization of visual scoring is desirable. Nevertheless, the analysis demonstrates that visual scoring is a reliable way of analysing DNA migration in comets.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"253-263"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876699","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":"Long-term cryopreservation of potassium bromate positive assay controls for measurement of oxidatively damaged DNA by the Fpg-modified comet assay: results from the hCOMET ring trial.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Adriana Rodriguez-Garraus,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Sara Ristori,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo',&nbsp;Patrizia Riso,&nbsp;Congying Zheng,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead020","DOIUrl":"10.1093/mutage/gead020","url":null,"abstract":"<p><p>The formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay is widely used for the measurement of oxidatively generated damage to DNA. However, there has not been a recommended long-term positive control for this version of the comet assay. We have investigated potassium bromate as a positive control for the Fpg-modified comet assay because it generates many Fpg-sensitive sites with a little concurrent generation of DNA strand breaks. Eight laboratories used the same procedure for the treatment of monocytic THP-1 cells with potassium bromate (0, 0.5, 1.5, and 4.5 mM) and subsequent cryopreservation in a freezing medium consisting of 50% foetal bovine serum, 40% RPMI-1640 medium, and 10% dimethyl sulphoxide. The samples were analysed by the Fpg-modified comet assay three times over a 3-year period. All laboratories obtained a positive concentration-response relationship in cryopreserved samples (linear regression coefficients ranging from 0.79 to 0.99). However, there was a wide difference in the levels of Fpg-sensitive sites between the laboratory with the lowest (4.2% Tail DNA) and highest (74% Tail DNA) values in THP-1 cells after exposure to 4.5 mM KBrO3. In an attempt to assess sources of inter-laboratory variation in Fpg-sensitive sites, comet images from one experiment in each laboratory were forwarded to a central laboratory for visual scoring. There was high consistency between measurements of %Tail DNA values in each laboratory and the visual score of the same comets done in the central laboratory (r = 0.98, P < 0.001, linear regression). In conclusion, the results show that potassium bromate is a suitable positive comet assay control.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"264-272"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042290","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":"Inter-laboratory variation in measurement of DNA damage by the alkaline comet assay in the hCOMET ring trial.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Miguel Collia,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Sara Ristori,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo,&nbsp;Patrizia Riso,&nbsp;Congying Zheng,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead014","DOIUrl":"10.1093/mutage/gead014","url":null,"abstract":"<p><p>The comet assay is a simple and versatile method for measurement of DNA damage in eukaryotic cells. More specifically, the assay detects DNA migration from agarose gel-embedded nucleoids, which depends on assay conditions and the level of DNA damage. Certain steps in the comet assay procedure have substantial impact on the magnitude of DNA migration (e.g. electric potential and time of electrophoresis). Inter-laboratory variation in DNA migration levels occurs because there is no agreement on optimal assay conditions or suitable assay controls. The purpose of the hCOMET ring trial was to test potassium bromate (KBrO3) as a positive control for the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay. To this end, participating laboratories used semi-standardized protocols for cell culture (i.e. cell culture, KBrO3 exposure, and cryopreservation of cells) and comet assay procedures, whereas the data acquisition was not standardized (i.e. staining of comets and image analysis). Segregation of the total variation into partial standard deviation (SD) in % Tail DNA units indicates the importance of cell culture procedures (SD = 10.9), comet assay procedures (SD = 12.3), staining (SD = 7.9) and image analysis (SD = 0.5) on the overall inter-laboratory variation of DNA migration (SD = 18.2). Future studies should assess sources of variation in each of these steps. On the positive side, the hCOMET ring trial demonstrates that KBrO3 is a robust positive control for the Fpg-modified comet assay. In conclusion, the hCOMET ring trial has demonstrated a high reproducibility of detecting genotoxic effects by the comet assay, but inter-laboratory variation of DNA migration levels is a concern.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"283-294"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876152","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 strand break levels in cryopreserved mononuclear blood cell lines measured by the alkaline comet assay: results from the hCOMET ring trial.","authors":"Peter Møller,&nbsp;Amaya Azqueta,&nbsp;Adriana Rodriguez-Garraus,&nbsp;Tamara Bakuradze,&nbsp;Elke Richling,&nbsp;Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper,&nbsp;Victoria Claudino Bastos,&nbsp;Sabine A S Langie,&nbsp;Annie Jensen,&nbsp;Sara Ristori,&nbsp;Francesca Scavone,&nbsp;Lisa Giovannelli,&nbsp;Maria Wojewódzka,&nbsp;Marcin Kruszewski,&nbsp;Vanessa Valdiglesias,&nbsp;Blanca Laffon,&nbsp;Carla Costa,&nbsp;Solange Costa,&nbsp;João Paulo Teixeira,&nbsp;Mirko Marino,&nbsp;Cristian Del Bo',&nbsp;Patrizia Riso,&nbsp;Congying Zhang,&nbsp;Sergey Shaposhnikov,&nbsp;Andrew Collins","doi":"10.1093/mutage/gead019","DOIUrl":"10.1093/mutage/gead019","url":null,"abstract":"<p><p>The comet assay is widely used in biomonitoring studies for the analysis of DNA damage in leukocytes and peripheral blood mononuclear cells. Rather than processing blood samples directly, it can be desirable to cryopreserve whole blood or isolated cells for later analysis by the comet assay. However, this creates concern about artificial accumulation of DNA damage during cryopreservation. In this study, 10 laboratories used standardized cryopreservation and thawing procedures of monocytic (THP-1) or lymphocytic (TK6) cells. Samples were cryopreserved in small aliquots in 50% foetal bovine serum, 40% cell culture medium, and 10% dimethyl sulphoxide. Subsequently, cryopreserved samples were analysed by the standard comet assay on three occasions over a 3-year period. Levels of DNA strand breaks in THP-1 cells were increased (four laboratories), unaltered (four laboratories), or decreased (two laboratories) by long-term storage. Pooled analysis indicates only a modest positive association between storage time and levels of DNA strand breaks in THP-1 cells (0.37% Tail DNA per year, 95% confidence interval: -0.05, 0.78). In contrast, DNA strand break levels were not increased by cryopreservation in TK6 cells. There was inter-laboratory variation in levels of DNA strand breaks in THP-1 cells (SD = 3.7% Tail DNA) and TK6 reference sample cells (SD = 9.4% Tail DNA), whereas the intra-laboratory residual variation was substantially smaller (i.e. SD = 0.4%-2.2% Tail DNA in laboratories with the smallest and largest variation). In conclusion, the study shows that accumulation of DNA strand breaks in cryopreserved mononuclear blood cell lines is not a matter of concern.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"273-282"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060071","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":"Obituary to John Ashby (19 April 1943-03 October 2022).","authors":"David Kirkland,&nbsp;George Douglas","doi":"10.1093/mutage/gead026","DOIUrl":"10.1093/mutage/gead026","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"251-252"},"PeriodicalIF":2.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10388184","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":"Next Generation Sequencing Workshop at the Royal Society of Medicine (London, May 2022): how genomics is on the path to modernizing genetic toxicology.","authors":"Anthony M Lynch, Thalita B Zanoni, Jesse J Salk, Inigo Martincorena, Robert R Young, Jill Kucab, Charles C Valentine, Carole Yauk, Patricia A Escobar, Kristine L Witt, Roland Frötschl, Simon H Reed, Anne Ashford","doi":"10.1093/mutage/gead012","DOIUrl":"10.1093/mutage/gead012","url":null,"abstract":"<p><p>The use of error-corrected Next Generation Sequencing (ecNG) to determine mutagenicity has been a subject of growing interest and potentially a disruptive technology that could supplement, and in time, replace current testing paradigms in preclinical safety assessment. Considering this, a Next Generation Sequencing Workshop was held at the Royal Society of Medicine in London in May 2022, supported by the United Kingdom Environmental Mutagen Society (UKEMS) and TwinStrand Biosciences (WA, USA), to discuss progress and future applications of this technology. In this meeting report, the invited speakers provide an overview of the Workshop topics covered and identify future directions for research. In the area of somatic mutagenesis, several speakers reviewed recent progress made with correlating ecNGS to classic in vivo transgenic rodent mutation assays as well as exploring the use of this technology directly in humans and animals, and in complex organoid models. Additionally, ecNGS has been used for detecting off-target effects of gene editing tools and emerging data suggest ecNGS potential to measure clonal expansion of cells carrying mutations in cancer driver genes as an early marker of carcinogenic potential and for direct human biomonitoring. As such, the workshop demonstrated the importance of raising awareness and support for advancing the science of ecNGS for mutagenesis, gene editing, and carcinogenesis research. Furthermore, the potential of this new technology to contribute to advances in drug and product development and improve safety assessment was extensively explored.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"192-200"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotoxicity of cytokines at chemotherapy-induced 'storm' concentrations in a model of the human bone marrow.","authors":"Harshini S H Asurappulige,&nbsp;Adam D Thomas,&nbsp;H Ruth Morse","doi":"10.1093/mutage/gead018","DOIUrl":"10.1093/mutage/gead018","url":null,"abstract":"<p><p>Donor cell leukaemia (DCL) is a complication of haematopoietic stem cell transplantation where donated cells become malignant within the patient's bone marrow. As DCL predominates as acute myeloid leukaemia, we hypothesized that the cytokine storm following chemotherapy played a role in promoting and supporting leukaemogenesis. Cytokines have also been implicated in genotoxicity; thus, we explored a cell line model of the human bone marrow (BM) to secrete myeloid cytokines following drug treatment and their potential to induce micronuclei. HS-5 human stromal cells were exposed to mitoxantrone (MTX) and chlorambucil (CHL) and, for the first time, were profiled for 80 cytokines using an array. Fifty-four cytokines were detected in untreated cells, of which 24 were upregulated and 10 were downregulated by both drugs. FGF-7 was the lowest cytokine to be detected in both untreated and treated cells. Eleven cytokines not detected at baseline were detected following drug exposure. TNFα, IL6, GM-CSF, G-CSF, and TGFβ1 were selected for micronuclei induction. TK6 cells were exposed to these cytokines in isolation and in paired combinations. Only TNFα and TGFβ1 induced micronuclei at healthy concentrations, but all five cytokines induced micronuclei at storm levels, which was further increased when combined in pairs. Of particular concern was that some combinations induced micronuclei at levels above the mitomycin C positive control; however, most combinations were less than the sum of micronuclei induced following exposure to each cytokine in isolation. These data infer a possible role for cytokines through chemotherapy-induced cytokine storm, in the instigation and support of leukaemogenesis in the BM, and implicate the need to evaluate individuals for variability in cytokine secretion as a potential risk factor for complications such as DCL.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"201-215"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/09/gead018.PMC10448863.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of mobile phone-specific electromagnetic fields on DNA damage caused by occupationally relevant exposures: results of ex vivo experiments with peripheral blood mononuclear cells from different demographic groups.","authors":"Miroslav Mišík,&nbsp;Michael Kundi,&nbsp;Nadine Worel,&nbsp;Franziska Ferk,&nbsp;Hans-Peter Hutter,&nbsp;Michael Grusch,&nbsp;Armen Nersesyan,&nbsp;Denise Herrera Morales,&nbsp;Siegfried Knasmueller","doi":"10.1093/mutage/gead022","DOIUrl":"10.1093/mutage/gead022","url":null,"abstract":"<p><p>The aim of this study was to investigate if age and body mass of humans have an impact on the DNA-damaging properties of high-frequency mobile phone-specific electromagnetic fields (HF-EMF, 1950 MHz, universal mobile telecommunications system, UMTS signal) and if this form of radiation has an impact on the genotoxic effects of occupationally relevant exposures. Pooled peripheral blood mononuclear cells (PBMC) from three groups [young normal weight, young obese (YO), and older age normal weight individuals] were exposed to different doses of HF-EMF (0.25, 0.5, and 1.0 W/kg specific absorption rate-SAR) and simultaneously or sequentially to different chemicals which cause DNA damage (CrO3, NiCl2, benzo[a]pyrene diol epoxide-BPDE, and 4-nitroquinoline 1-oxide-4NQO) via different molecular mechanisms. We found no difference in regard to the background values in the three groups but a significant increase of DNA damage (81% without and 36% with serum) in cells from old participants after radiation with 1.0 W/kg SAR 16 h. In combined treatment experiments we found no impact of the UMTS signal on chemically induced DNA damage in the different groups in general. However, a moderate decrease of DNA damage was seen in simultaneous treatment experiments with BPDE and 1.0 W/kg SAR in the YO group (decline 18%). Taken together our findings indicate that HF-EMF cause DNA damage in PBMC from older subjects (69.1 years). Furthermore, they show that the radiation does not increase induction of DNA damage by occupationally relevant chemicals.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"227-237"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/b5/gead022.PMC10448860.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10072483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotoxicity by rapeseed methyl ester and hydrogenated vegetable oil combustion exhaust products in lung epithelial (A549) cells.","authors":"Monika Hezareh Rothmann,&nbsp;Peter Møller,&nbsp;Yona J Essig,&nbsp;Louise Gren,&nbsp;Vilhelm B Malmborg,&nbsp;Martin Tunér,&nbsp;Joakim Pagels,&nbsp;Annette M Krais,&nbsp;Martin Roursgaard","doi":"10.1093/mutage/gead016","DOIUrl":"10.1093/mutage/gead016","url":null,"abstract":"<p><p>Biofuel is an attractive substitute for petrodiesel because of its lower environmental footprint. For instance, the polycyclic aromatic hydrocarbons (PAH) emission per fuel energy content is lower for rapeseed methyl ester (RME) than for petrodiesel. This study assesses genotoxicity by extractable organic matter (EOM) of exhaust particles from the combustion of petrodiesel, RME, and hydrogenated vegetable oil (HVO) in lung epithelial (A549) cells. Genotoxicity was assessed as DNA strand breaks by the alkaline comet assay. EOM from the combustion of petrodiesel and RME generated the same level of DNA strand breaks based on the equal concentration of total PAH (i.e. net increases of 0.13 [95% confidence interval (CI): 0.002, 0.25, and 0.12 [95% CI: 0.01, 0.24] lesions per million base pairs, respectively). In comparison, the positive control (etoposide) generated a much higher level of DNA strand breaks (i.e. 0.84, 95% CI: 0.72, 0.97) lesions per million base pairs. Relatively low concentrations of EOM from RME and HVO combustion particles (<116 ng/ml total PAH) did not cause DNA strand breaks in A549 cells, whereas benzo[a]pyrene and PAH-rich EOM from petrodiesel combusted using low oxygen inlet concentration were genotoxic. The genotoxicity was attributed to high molecular weight PAH isomers with 5-6 rings. In summary, the results show that EOM from the combustion of petrodiesel and RME generate the same level of DNA strand breaks on an equal total PAH basis. However, the genotoxic hazard of engine exhaust from on-road vehicles is lower for RME than petrodiesel because of lower PAH emission per fuel energy content.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"238-249"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119573","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":"Current status and future challenges of genotoxicity OECD Test Guidelines for nanomaterials: a workshop report.","authors":"Shareen H Doak,&nbsp;Cristina Andreoli,&nbsp;Michael J Burgum,&nbsp;Qasim Chaudhry,&nbsp;Eric A J Bleeker,&nbsp;Cecilia Bossa,&nbsp;Josefa Domenech,&nbsp;Damjana Drobne,&nbsp;Valerie Fessard,&nbsp;Nina Jeliazkova,&nbsp;Eleonora Longhin,&nbsp;Elise Rundén-Pran,&nbsp;Maciej Stepnik,&nbsp;Naouale El Yamani,&nbsp;Julia Catalán,&nbsp;Maria Dusinska","doi":"10.1093/mutage/gead017","DOIUrl":"10.1093/mutage/gead017","url":null,"abstract":"<p><p>Genotoxicity testing for nanomaterials remains challenging as standard testing approaches require some adaptation, and further development of nano-specific OECD Test Guidelines (TGs) and Guidance Documents (GDs) are needed. However, the field of genotoxicology continues to progress and new approach methodologies (NAMs) are being developed that could provide relevant information on the range of mechanisms of genotoxic action that may be imparted by nanomaterials. There is a recognition of the need for implementation of new and/or adapted OECD TGs, new OECD GDs, and utilization of NAMs within a genotoxicity testing framework for nanomaterials. As such, the requirements to apply new experimental approaches and data for genotoxicity assessment of nanomaterials in a regulatory context is neither clear, nor used in practice. Thus, an international workshop with representatives from regulatory agencies, industry, government, and academic scientists was convened to discuss these issues. The expert discussion highlighted the current deficiencies that exist in standard testing approaches within exposure regimes, insufficient physicochemical characterization, lack of demonstration of cell or tissue uptake and internalization, and limitations in the coverage of genotoxic modes of action. Regarding the latter aspect, a consensus was reached on the importance of using NAMs to support the genotoxicity assessment of nanomaterials. Also highlighted was the need for close engagement between scientists and regulators to (i) provide clarity on the regulatory needs, (ii) improve the acceptance and use of NAM-generated data, and (iii) define how NAMs may be used as part of weight of evidence approaches for use in regulatory risk assessments.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 4","pages":"183-191"},"PeriodicalIF":2.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}