Environmental and Molecular Mutagenesis最新文献

{"title":"Decrease of air pollution during lockdown in Tuscany (Italy): An effect on sperm DNA fragmentation?","authors":"Costanza Calamai,&nbsp;Oumaima Ammar,&nbsp;Sara Marchiani,&nbsp;Selene Degl'Innocenti,&nbsp;Marisa Fino,&nbsp;Lorenzo Righi,&nbsp;Sara Dabizzi,&nbsp;Mario Maggi,&nbsp;Elisabetta Baldi,&nbsp;Linda Vignozzi,&nbsp;Monica Muratori","doi":"10.1002/em.22530","DOIUrl":"10.1002/em.22530","url":null,"abstract":"<p>In March 2020, the Italian government imposed a national lockdown which was almost completely removed in June 2020. Due to the abrupt stop of human activities, emissions of air pollutants decreased. Air pollution is an environmental risk factor for noncommunicable disease and mortality. Emerging evidence also suggests a role in male infertility. In this study, we compared sperm DNA fragmentation (sDF) levels and conventional semen parameters between subjects undergoing sDF determination and routine semen analysis in a single Italian centre, during about 6 months before (<i>N</i> = 119) and after lockdown (<i>N</i> = 105). After lockdown, we found an improvement of sperm progressive motility (48.00[38.50–58.00]% vs. 42.00[33.00–53.00]%) and sDF levels (as total: 24.79[18.33–33.97]% vs. 35.02[25.04–45.73]%, <i>p</i> &lt; .001; brighter: 14.02[10.69–17.93]% vs 18.54[13.58–25.82]%, <i>p</i> &lt; .001 and dimmer sDF: 9.24[5.64–15.78]% vs. 12.24[8.08–19.10]%, <i>p</i> &lt; .01), mirrored by a decrease of leukocyte semen concentration (<i>p</i> &lt; .01). The improvement of sperm motility and DNA quality was maintained after adjusting for leukocyte concentration and several conditions known to affect sperm motility and/or sDF levels. With a significant decrease in air pollution observed in Tuscany during and after lockdown, associated improvement in sperm motility and DNA quality in patients referred to the infertility clinic is suggestive of the potential role of air pollution in male infertility.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 3","pages":"148-158"},"PeriodicalIF":2.8,"publicationDate":"2023-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9735202","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":"Remembering Radim J. Šrám","authors":"David M. DeMarini,&nbsp;Miriam C. Poirier,&nbsp;Michael D. Waters,&nbsp;Nina Holland","doi":"10.1002/em.22528","DOIUrl":"10.1002/em.22528","url":null,"abstract":"","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 2","pages":"70-71"},"PeriodicalIF":2.8,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762519","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":"Quantitative interpretation of ToxTracker dose–response data for potency comparisons and mode-of-action determination","authors":"Lorrie Boisvert,&nbsp;Remco Derr,&nbsp;Torben Osterlund,&nbsp;Giel Hendriks,&nbsp;Inger Brandsma","doi":"10.1002/em.22525","DOIUrl":"10.1002/em.22525","url":null,"abstract":"<p>ToxTracker is an in vitro mammalian stem cell-based reporter assay that detects activation of specific cellular signaling pathways (DNA damage, oxidative stress, and/or protein damage) upon chemical exposure using flow cytometry. Here we used quantitative methods to empirically analyze historical control data, and dose–response data across a wide range of reference chemicals. First, we analyzed historical control data to define a fold-change threshold for identification of a significant positive response. Next, we used the benchmark dose (BMD) combined-covariate approach for potency ranking of a set of more than 120 compounds; the BMD values were used for comparative identification of the most potent inducers of each reporter. Lastly, we used principal component analysis (PCA) to investigate functional and statistical relationships between the ToxTracker reporters. The PCA results, based on the BMD results for all substances, indicated that the DNA damage (<i>Rtkn</i>, <i>Bscl2</i>) and p53 (<i>Btg2</i>) reporters are functionally complementary and indicative of genotoxic stress. The oxidative stress (<i>Srxn1</i> and <i>Blvrb</i>) and protein stress (<i>Ddit3</i>) reporters are independent indicators of cellular stress, and essential for toxicological profiling using the ToxTracker assay. Overall, dose–response modeling of multivariate ToxTracker data can be used for potency ranking and mode-of-action determination. In the future, IVIVE (in vitro to in vivo extrapolation) methods can be employed to determine in vivo AED (administered equivalent dose) values that can in turn be used for human health risk assessment.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 2","pages":"132-143"},"PeriodicalIF":2.8,"publicationDate":"2023-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487417","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":"Assessing testicular germ cell DNA damage in the comet assay; introduction of a proof-of-concept","authors":"Yvette Dirven,&nbsp;Dag Markus Eide,&nbsp;Erika Witasp Henriksson,&nbsp;Rune Hjorth,&nbsp;Anoop Kumar Sharma,&nbsp;Anne Graupner,&nbsp;Gunnar Brunborg,&nbsp;Jarle Ballangby,&nbsp;Anne Mette Zenner Boisen,&nbsp;Stellan Swedmark,&nbsp;Kristine Bjerve Gützkow,&nbsp;Ann-Karin Olsen","doi":"10.1002/em.22527","DOIUrl":"10.1002/em.22527","url":null,"abstract":"<p>The <i>in vivo</i> comet assay is widely used to measure genotoxicity; however, the current OECD test guideline (TG 489) does not recommend using the assay to assess testicular germ cells, due to the presence of testicular somatic cells. An adapted approach to specifically assess testicular germ cells within the comet assay is certainly warranted, considering regulatory needs for germ cell-specific genotoxicity data in relation to the increasing global production of and exposure to potentially hazardous chemicals. Here, we provide a proof-of-concept to selectively analyze round spermatids and primary spermatocytes, distinguishing them from other cells of the testicle. Utilizing the comet assay recordings of DNA content (total fluorescence intensity) and DNA damage (% tail intensity) of individual comets, we developed a framework to distinguish testicular cell populations based on differences in DNA content/ploidy and appearance. Haploid round spermatid comets are identified through (1) visual inspection of DNA content distributions, (2) setting DNA content thresholds, and (3) modeling DNA content distributions using a normal mixture distribution function. We also describe an approach to distinguish primary spermatocytes during comet scoring, based on their high DNA content and large physical size. Our concept allows both somatic and germ cells to be analyzed in the same animal, adding a versatile, sensitive, rapid, and resource-efficient assay to the limited genotoxicity assessment toolbox for germ cells. An adaptation of TG 489 facilitates accumulation of valuable information regarding distribution of substances to germ cells and their potential for inducing germ cell gene mutations and structural chromosomal aberrations.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 2","pages":"88-104"},"PeriodicalIF":2.8,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471064","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":"Intergenerational arsenic exposure on the mouse epigenome and metabolic physiology","authors":"Mathia L. Colwell,&nbsp;Nicole Flack,&nbsp;Amanda Rezabek,&nbsp;Christopher Faulk","doi":"10.1002/em.22526","DOIUrl":"10.1002/em.22526","url":null,"abstract":"<p>Inorganic arsenic (iAs) is one of the largest toxic exposures to impact humanity worldwide. Exposure to iAs during pregnancy may disrupt the proper remodeling of the epigenome of F1 developing offspring and potentially their F2 grand-offspring via disruption of fetal primordial germ cells (PGCs). There is a limited understanding between the correlation of disease phenotype and methylation profile within offspring of both generations and whether it persists to adulthood. Our study aims to understand the intergenerational effects of in utero iAs exposure on the epigenetic profile and onset of disease phenotypes within F1 and F2 adult offspring, despite the lifelong absence of direct arsenic exposure within these generations. We exposed F0 female mice (C57BL6/J) to the following doses of iAs in drinking water 2 weeks before pregnancy until the birth of the F1 offspring: 1, 10, 245, and 2300 ppb. We found sex- and dose-specific changes in weight and body composition that persist from early time to adulthood within both generations. Fasting blood glucose challenge suggests iAs exposure causes dysregulation of glucose metabolism, revealing generational, exposure, and sex-specific differences. Toward understanding the mechanism, genome-wide DNA methylation data highlights exposure-specific patterns in liver, finding dysregulation within genes associated with cancer, T2D, and obesity. We also identified regions containing persistently differentially methylated CpG sites between F1 and F2 generations. Our results indicate the F1 developing embryos and their PGCs, which will result in F2 progeny, retain epigenetic damage established during the prenatal period and are associated with adult metabolic dysfunction.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 2","pages":"72-87"},"PeriodicalIF":2.8,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9440080","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":"Genotoxic repercussion of high-intensity radiation (x-rays) on hospital radiographers","authors":"Haripriya Kuchi Bhotla,&nbsp;Balamuralikrishnan Balasubramanian,&nbsp;Kannan R. R. Rengasamy,&nbsp;Vijaya Anand Arumugam,&nbsp;Karthick Kumar Alagamuthu,&nbsp;Vadivalagan Chithravel,&nbsp;Aditi Chaudhary,&nbsp;Amer M. Alanazi,&nbsp;Manikantan Pappuswamy,&nbsp;Arun Meyyazhagan","doi":"10.1002/em.22523","DOIUrl":"10.1002/em.22523","url":null,"abstract":"<p>Recent technological advances in the medical field have increased the plausibility of exposing humans to high-intensity wavelength radiations like x-rays and gamma rays while diagnosing or treating specific medical maladies. These radiations induce nucleotide changes and chromosomal alterations in the exposed population, intentionally or accidentally. A radiological investigation is regularly used in identifying the disease, especially by the technicians working in intensive care units. The current study observes the genetic damages like chromosomal abnormalities (CA) in clinicians who are occupationally exposed to high-intensity radiations (x-rays) at their workplaces using universal cytogenetic tools like micronucleus assay (MN), sister chromatid exchange and comet assay. The study was conducted between 100 exposed practitioners from the abdominal scanning, chest scanning, cranial and orthopedic or bone scanning department and age-matched healthy controls. We observed a slightly higher rate of MN and CA (<i>p</i> &lt; .05) in orthopedic and chest department practitioners than in other departments concerning increasing age and duration of exposure at work. Our results emphasize taking extra precautionary measures in clinical and hospital radiation laboratories to protect the practitioners.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 2","pages":"123-131"},"PeriodicalIF":2.8,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9499697","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":"The impact of environmental contaminants on extracellular vesicles and their key molecular regulators: A literature and database-driven review","authors":"Celeste K. Carberry,&nbsp;Julia E. Rager","doi":"10.1002/em.22522","DOIUrl":"10.1002/em.22522","url":null,"abstract":"<p>Exposure to environmental chemicals is now well recognized as a significant factor contributing to the global burden of disease; however, there remain critical gaps in understanding the types of biological mechanisms that link environmental chemicals to adverse health outcomes. One type of mechanism that remains understudied involves extracellular vesicles (EVs), representing small cell-derived particles capable of carrying molecular signals such as RNAs, miRNAs, proteins, lipids, and chemicals through biological fluids and imparting beneficial, neutral, or negative effects on target cells. In fact, evidence is just now starting to grow that supports the role of EVs in various disease etiologies. This review aims to (1) Provide a landscape of the current understanding of the functional relationship between EVs and environmental chemicals; (2) Summarize current knowledge of EV regulatory processes including production, packaging, and release; and (3) Conduct a database-driven analysis of known chemical–gene interactions to predict and prioritize environmentally relevant chemicals that may impact EV regulatory genes and thus EV regulatory processes. This approach to predicting environmentally relevant chemicals that may alter EVs provides a novel method for evidence-based hypothesis generation for future studies evaluating the link between environmental exposures and EVs.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 1","pages":"50-66"},"PeriodicalIF":2.8,"publicationDate":"2022-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9115707","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":"Quantitative in vitro to in vivo extrapolation of genotoxicity data provides protective estimates of in vivo dose","authors":"Marc A. Beal,&nbsp;Marc Audebert,&nbsp;Tara Barton-Maclaren,&nbsp;Hannah Battaion,&nbsp;Jeffrey C. Bemis,&nbsp;Xuefei Cao,&nbsp;Connie Chen,&nbsp;Stephen D. Dertinger,&nbsp;Roland Froetschl,&nbsp;Xiaoqing Guo,&nbsp;George Johnson,&nbsp;Giel Hendriks,&nbsp;Laure Khoury,&nbsp;Alexandra S. Long,&nbsp;Stefan Pfuhler,&nbsp;Raja S. Settivari,&nbsp;Shamika Wickramasuriya,&nbsp;Paul White","doi":"10.1002/em.22521","DOIUrl":"10.1002/em.22521","url":null,"abstract":"<p>Genotoxicity assessment is a critical component in the development and evaluation of chemicals. Traditional genotoxicity assays (i.e., mutagenicity, clastogenicity, and aneugenicity) have been limited to dichotomous hazard classification, while other toxicity endpoints are assessed through quantitative determination of points-of-departures (PODs) for setting exposure limits. The more recent higher-throughput in vitro genotoxicity assays, many of which also provide mechanistic information, offer a powerful approach for determining defined PODs for potency ranking and risk assessment. In order to obtain relevant human dose context from the in vitro assays, in vitro to in vivo extrapolation (IVIVE) models are required to determine what dose would elicit a concentration in the body demonstrated to be genotoxic using in vitro assays. Previous work has demonstrated that application of IVIVE models to in vitro bioactivity data can provide PODs that are protective of human health, but there has been no evaluation of how these models perform with in vitro genotoxicity data. Thus, the Genetic Toxicology Technical Committee, under the Health and Environmental Sciences Institute, conducted a case study on 31 reference chemicals to evaluate the performance of IVIVE application to genotoxicity data. The results demonstrate that for most chemicals considered here (20/31), the PODs derived from in vitro data and IVIVE are health protective relative to in vivo PODs from animal studies. PODs were also protective by assay target: mutations (8/13 chemicals), micronuclei (9/12), and aneugenicity markers (4/4). It is envisioned that this novel testing strategy could enhance prioritization, rapid screening, and risk assessment of genotoxic chemicals.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 2","pages":"105-122"},"PeriodicalIF":2.8,"publicationDate":"2022-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9112205","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":"Bladder cancer tissue-derived exosomes suppress ferroptosis of T24 bladder cancer cells by transporting miR-217","authors":"Zhong-Ming Huang,&nbsp;Hai Wang,&nbsp;Zhi-Gang Ji","doi":"10.1002/em.22520","DOIUrl":"10.1002/em.22520","url":null,"abstract":"<p>It has been reported that miR-217 can inhibit the oncogenic activity and progression of bladder cancer (BCa) cells, but it has not been explored whether miR-217 is involved in the regulation of ferroptosis. In the present study, RNA transfection, real-time PCR, flow cytometry, Western blotting assays, immunofluorescence and ELISA were performed to explore the effects and mechanisms of miR-217 in BCa tissue-derived exosomes. We found that extracellular fluid from bladder cancer tissue promoted the growth and miR-217 expression of T24 cells and inhibited ferroptosis. MiR-217 was confirmed to inhibit ferroptosis in bladder cancer cells by RNA interference and functional assays. By cell membrane fluorescence probe (CM-Dil) labeling, inhibiting exosome secretion by GW4689 and exosome extraction, we determined that BCa tissue-derived exosomes transport miR-217 into T24 cells. Culture of T24 cells with extracellular fluid after RNA interference showed that exosomes carrying miR-217 derived from BCa tissues inhibited ferroptosis of T24 cells. We conclude that bladder cancer tissue-derived exosomes inhibit ferroptosis of T24 bladder cancer cells by transporting miR-217. The results of our study provide a new insight into the progression of bladder cancer.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 1","pages":"39-49"},"PeriodicalIF":2.8,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9470500","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":"Mutagenicity of the organic fraction of World Trade Center dust","authors":"David M. DeMarini,&nbsp;Sarah H. Warren,&nbsp;Lance R. Brooks","doi":"10.1002/em.22519","DOIUrl":"10.1002/em.22519","url":null,"abstract":"<p>Most studies of the health effects and chemical characterization of the dust resulting from the catastrophic collapse of the World Trade Center (WTC) on September 11, 2001, have focused on the large inorganic fraction of the dust; however, chemical analyses have identified mutagens and carcinogens in the smaller organic fraction. Here, we determined the mutagenicity of the organic fraction of WTC dust in <i>Salmonella</i>. Only 0.74% of the mass of the particulate matter (PM) &lt;53 μm in diameter was extractable organic matter (EOM). Because the EOM was 10 times more mutagenic in TA100 +S9 than in TA98 +S9 and was negative in TA98 −S9, we inferred, respectively, that polycyclic aromatic hydrocarbons (PAHs) played a role in the mutagenicity and not nitroarenes. In TA98 +S9, the mutagenic potency of the EOM (0.1 revertant/μg EOM) was within the range of EOMs from air and combustion emissions. However, the EOM-based mutagenic potency of the particles (0.0007 revertants/μg PM) was 1–2 orders of magnitude lower than values from a review of 50 combustion emissions and various air samples. We calculated that 37 PAHs analyzed previously in WTC EOM were 5.4% of the EOM mass and 0.04% of the PM mass; some air contained 0.3 μg WTC EOM/m³ (0.02 μg PAHs/m³). Populations exposed to WTC dust have elevated levels of prostate and thyroid cancer but not lung cancer. Our data support earlier estimates that PAH-associated cancer risk among this population, for example, PAH-associated lung cancer, was unlikely to be significantly elevated relative to background PAH exposures.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 1","pages":"16-25"},"PeriodicalIF":2.8,"publicationDate":"2022-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9366369","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}