Genes and Environment最新文献

{"title":"Split MutT prevents the mutator phenotype of mutT-deficient Escherichia coli.","authors":"Hiroyuki Kamiya","doi":"10.1186/s41021-024-00314-8","DOIUrl":"https://doi.org/10.1186/s41021-024-00314-8","url":null,"abstract":"<p><strong>Background: </strong>The Escherichia coli MutT (NudA) protein catalyzes the hydrolysis of an oxidized form of dGTP, 8-oxo-7,8-dihydro-dGTP (8-hydroxy-dGTP), and the spontaneous mutation frequency is elevated in E. coli cells deficient in the mutT gene.</p><p><strong>Results: </strong>A split MutT, comprising the N-terminal (residues 1-95) and C-terminal (residues 96-129) peptides, was designed based on the known tertiary structure and linker insertion mutagenesis experiments. The mutator phenotype was complemented when the two peptides were separately expressed in mutT E. coli cells.</p><p><strong>Conclusions: </strong>These results indicated that this split MutT functions as a nucleotide pool sanitization enzyme in vivo.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"19"},"PeriodicalIF":2.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389814","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":"PARP-1 negatively regulates nucleolar protein pool and mitochondrial activity: a cell protective mechanism.","authors":"Atanu Ghorai, Soumajit Saha, Basuthkar J Rao","doi":"10.1186/s41021-024-00312-w","DOIUrl":"https://doi.org/10.1186/s41021-024-00312-w","url":null,"abstract":"<p><strong>Background: </strong>Poly(ADP-ribose) polymerase-1 (PARP-1) is a pan nuclear protein that utilizes NAD⁺ as a substrate for poly(ADP-ribosyl)ation reaction (PARylation), resulting in both auto-modification and the modification of its accepter proteins. Earlier reports suggested that several nucleolar proteins interact and colocalize with PARP-1, leading to their PARylation. However, whether PARP-1 has any role in nucleolar biogenesis and the functional relevance of such a role is still obscure.</p><p><strong>Results: </strong>Using PARP-1 depleted cells, we investigated the function of PARP-1 in maintaining the nucleolar morphology and protein levels under normal physiological conditions. Our results revealed that several nucleolar proteins like nucleolin, fibrillarin, and nucleophosmin get up-regulated when PARP-1 is depleted. Additionally, in line with the higher accumulation of nucleolin, stably depleted PARP-1 cells show lower activation of caspase-3, lesser annexin-V staining, and reduced accumulation of AIF in the nucleus upon induction of oxidative stress. Concurrently, PARP-1 silenced cells showed higher mitochondrial oxidative phosphorylation and more fragmented and intermediate mitochondria than the parental counterpart, suggesting higher metabolic activity for better survival.</p><p><strong>Conclusion: </strong>Based on our findings, we demonstrate that PARP-1 may have a role in regulating nucleolar protein levels and mitochondrial activity, thus maintaining the homeostasis between cell protective and cell death pathways, and such cell-protective mechanism could be implicated as the priming state of a pre-cancerous condition or tumour dormancy.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"18"},"PeriodicalIF":2.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284340","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":"Confirmation of Di(2-ethylhexyl) phthalate-induced micronuclei by repeated dose liver micronucleus assay: focus on evaluation of liver micronucleus assay in young rats.","authors":"Miyuki Shigano, Rie Takashima, Kensuke Satomoto, Henri Sales, Ryoko Harada, Shuichi Hamada","doi":"10.1186/s41021-024-00311-x","DOIUrl":"10.1186/s41021-024-00311-x","url":null,"abstract":"<p><strong>Background: </strong>Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in a wide variety of products, including medical devices. It is rapidly metabolized in the liver into various metabolites upon absorption through oral ingestion, dermal absorption, and inhalation. DEHP is classified as a non-genotoxic hepatocarcinogen in rodents, as its chronic exposure has been associated with the development of liver cancer in these animals, but most genotoxicity studies have been negative. Epidemiologic studies in humans suggest that long-term high intakes of DEHP may be a risk factor for liver dysfunction. The repeated-dose liver micronucleus (RDLMN) assay is a well-established method for assessing chromosomal changes caused by hepatic genotoxins and/or carcinogens. It is particularly valuable for detecting substances that undergo metabolic activation, especially when the metabolite has a short half-life or does not reach the bone marrow effectively. Therefore, we investigated whether the RDLMN assay could detect DEHP-induced micronucleus formation in the liver following a 14 or 28-day treatment.</p><p><strong>Results: </strong>We report that the RDLMN assay demonstrated an increased frequency of hepatic micronuclei in rats exposed to DEHP for 14 or 28 days. The increases in micronuclei correlated with hepatomegaly, an established response to phthalates in the liver. Conversely, no such increases were observed in the micronucleus assay using bone marrow from these rats.</p><p><strong>Conclusion: </strong>The detection of DEHP-induced micronuclei by the RDLMN assay suggests that this assay could detect the potential genotoxicity and hepatocarcinogenicity of DEHP. It also demonstrated the utility of the RDLMN assay in identifying metabolically activated hepatic carcinogens.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"17"},"PeriodicalIF":2.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046565","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":"Correction: LncRNA PVT1 induces apoptosis and inflammatory response of bronchial epithelial cells by regulating miR-30b-5p/BCL2L11 axis in COPD.","authors":"Taoli Fu, Hui Tian, Hui Rong, Ping Ai, Xiaoping Li","doi":"10.1186/s41021-024-00309-5","DOIUrl":"10.1186/s41021-024-00309-5","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"16"},"PeriodicalIF":2.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633092","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":"Mapping the influence of hydrocarbons mixture on molecular mechanisms, involved in breast and lung neoplasms: in silico toxicogenomic data-mining.","authors":"A'edah Abu-Bakar, Maihani Ismail, M Zaqrul Ieman Zulkifli, Nur Aini Sofiyya Zaini, Nur Izzah Abd Shukor, Sarahani Harun, Salmaan Hussain Inayat-Hussain","doi":"10.1186/s41021-024-00310-y","DOIUrl":"10.1186/s41021-024-00310-y","url":null,"abstract":"<p><strong>Background: </strong>Exposure to chemical mixtures inherent in air pollution, has been shown to be associated with the risk of breast and lung cancers. However, studies on the molecular mechanisms of exposure to a mixture of these pollutants, such as hydrocarbons, in the development of breast and lung cancers are scarce. We utilized in silico toxicogenomic analysis to elucidate the molecular pathways linked to both cancers that are influenced by exposure to a mixture of selected hydrocarbons. The Comparative Toxicogenomics Database and Cytoscape software were used for data mining and visualization.</p><p><strong>Results: </strong>Twenty-five hydrocarbons, common in air pollution with carcinogenicity classification of 1 A/B or 2 (known/presumed or suspected human carcinogen), were divided into three groups: alkanes and alkenes, halogenated hydrocarbons, and polyaromatic hydrocarbons. The in silico data-mining revealed 87 and 44 genes commonly interacted with most of the investigated hydrocarbons are linked to breast and lung cancer, respectively. The dominant interactions among the common genes are co-expression, physical interaction, genetic interaction, co-localization, and interaction in shared protein domains. Among these genes, only 16 are common in the development of both cancers. Benzo(a)pyrene and tetrachlorodibenzodioxin interacted with all 16 genes. The molecular pathways potentially affected by the investigated hydrocarbons include aryl hydrocarbon receptor, chemical carcinogenesis, ferroptosis, fluid shear stress and atherosclerosis, interleukin 17 signaling pathway, lipid and atherosclerosis, NRF2 pathway, and oxidative stress response.</p><p><strong>Conclusions: </strong>Within the inherent limitations of in silico toxicogenomics tools, we elucidated the molecular pathways associated with breast and lung cancer development potentially affected by hydrocarbons mixture. Our findings indicate adaptive responses to oxidative stress and inflammatory damages are instrumental in the development of both cancers. Additionally, ferroptosis-a non-apoptotic programmed cell death driven by lipid peroxidation and iron homeostasis-was identified as a new player in these responses. Finally, AHR potential involvement in modulating IL-8, a critical gene that mediates breast cancer invasion and metastasis to the lungs, was also highlighted. A deeper understanding of the interplay between genes associated with these pathways, and other survival signaling pathways identified in this study, will provide invaluable knowledge in assessing the risk of inhalation exposure to hydrocarbons mixture. The findings offer insights into future in vivo and in vitro laboratory investigations that focus on inhalation exposure to the hydrocarbons mixture.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"15"},"PeriodicalIF":2.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563234","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":"Long noncoding RNA TMPO-AS1 upregulates BCAT1 expression to promote cell proliferation in nasopharyngeal carcinoma via microRNA let-7c-5p.","authors":"Huan Wang, Fuming Zhou, Jia Wan, Hong Yu, Jin Wang","doi":"10.1186/s41021-024-00308-6","DOIUrl":"https://doi.org/10.1186/s41021-024-00308-6","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNA (lncRNA) is a group of RNA transcripts that contribute to tumor development by post-transcriptionally regulating cancer-related genes. Nasopharyngeal carcinoma (NPC) is an epithelial tumor that occurs in the nasopharynx and is common in North Africa and Southeast Asia. The study investigated the functions of lncRNA TMPO-AS1 in NPC cell proliferation and apoptosis as well as its related competing endogenous RNA (ceRNA) mechanism.</p><p><strong>Methods: </strong>Candidate microRNA and genes that may regulated by TMPO-AS1 were predicted with the bioinformatic tool starBase. TMPO-AS1 expression in NPC tissue, cells, nuclear part, and cytoplasmic part was measured by RT-qPCR. MTT assay, EdU assay, and flow cytometry analysis were carried out to evaluate NPC cell viability, proliferation, and apoptosis, respectively. RNA immunoprecipitation assay and luciferase reporter assay were conducted to detect the binding between TMPO-AS1 and let-7c-5p or that between let-7c-5p and BCAT1.</p><p><strong>Results: </strong>TMPO-AS1 and BCAT1 showed high expression in NPC tissue and cells, while let-7c-5p was downregulated in NPC. The silencing of TMPO-AS1 suppressed NPC cell proliferation while promoting cell apoptosis. Moreover, TMPO-AS1 interacted with let-7c-5p and negatively regulated let-7c-5p expression. BCAT1 was a target of let-7c-5p and was inversely regulated by let-7c-5p in NPC cells. The repressive impact of TMPO-AS1 knockdown on NPC cell growth was countervailed by overexpressed BCAT1.</p><p><strong>Conclusion: </strong>TMPO-AS1 accelerates NPC cell proliferation and represses cell apoptosis by interacting with let-7c-5p to regulate BCAT1 expression.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"14"},"PeriodicalIF":2.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467488","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":"Rosmarinic acid, a natural polyphenol, has a potential pro-oxidant risk via NADH-mediated oxidative DNA damage.","authors":"Hatasu Kobayashi, Yuichiro Hirao, Shosuke Kawanishi, Shinya Kato, Yurie Mori, Mariko Murata, Shinji Oikawa","doi":"10.1186/s41021-024-00307-7","DOIUrl":"10.1186/s41021-024-00307-7","url":null,"abstract":"<p><strong>Background: </strong>Rosmarinic acid (RA) has a wide range of beneficial effects on human health. On the other hand, RA has been reported to induce metal-mediated reactive oxygen species (ROS) generation and DNA damage. However, its mechanism remains unknown. In this study, to clarify the underlying mechanism, we analyzed metal-mediated DNA damage in isolated DNA treated with RA and its analog isorinic acid.</p><p><strong>Results: </strong>RA plus Cu(II), but not Fe(III), significantly increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, an indicator of oxidative DNA damage, in calf thymus DNA. Furthermore, a comparison of the 8-oxodG formation induced by RA and its analog isorinic acid suggested that the catechol groups in RA could be associated with their abilities to form 8-oxodG. Interestingly, the 8-oxodG formation induced by RA and isorinic acid plus Cu(II) was markedly enhanced by the addition of NADH, an endogenous reductant. To elucidate the mechanism of RA plus Cu(II)-induced oxidative DNA damage, we examined DNA damage in ³²P-labeled DNA treated with RA in the presence of Cu(II). RA plus Cu(II) caused DNA cleavage, which was enhanced by piperidine treatment, suggesting that RA causes not only DNA strand breakage but also base modification. RA plus Cu(II)-induced DNA damage was inhibited by catalase (H₂O₂ scavenger), bathocuproine (Cu(I) chelator), and methional (scavenger of a variety of ROS other than ^•OH) but not by typical ^•OH scavengers and SOD, indicating the involvement of H₂O₂, Cu(I), and ROS other than ^•OH. DNA cleavage site analysis showing RA-induced site-specific DNA damage (frequently at thymine and some cytosine residues) supports the involvement of ROS other than ^•OH, because ^•OH causes DNA cleavage without site specificity. Based on these results, Cu(I) and H₂O₂ generation with concomitant RA autoxidation could lead to the production of Cu(I)-hydroperoxide, which induces oxidative DNA damage. o-Quinone and o-semiquinone radicals are likely to be again reduced to RA by NADH, which dramatically increases oxidative DNA damage, particularly at low concentrations of RA.</p><p><strong>Conclusions: </strong>In this study, physiologically relevant concentrations of RA effectively induced oxidative DNA damage in isolated DNA through redox cycle reactions with copper and NADH.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"13"},"PeriodicalIF":1.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237431","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":"Genome-wide somatic mutation analysis of sinonasal adenocarcinoma with and without wood dust exposure.","authors":"Lauri J Sipilä, Riku Katainen, Mervi Aavikko, Janne Ravantti, Iikki Donner, Rainer Lehtonen, Ilmo Leivo, Henrik Wolff, Reetta Holmila, Kirsti Husgafvel-Pursiainen, Lauri A Aaltonen","doi":"10.1186/s41021-024-00306-8","DOIUrl":"10.1186/s41021-024-00306-8","url":null,"abstract":"<p><strong>Background: </strong>Sinonasal adenocarcinoma is a rare cancer, encompassing two different entities, the intestinal-type sinonasal adenocarcinoma (ITAC) and the non-intestinal-type sinonasal adenocarcinoma (non-ITAC). Occurrence of ITAC is strongly associated with exposure to hardwood dusts. In countries with predominant exposure to softwood dust the occurrence of sinonasal adenocarcinomas is lower and the relative amount of non-ITACs to ITACs is higher. The molecular mechanisms behind the tumorigenic effects of wood dust remain largely unknown.</p><p><strong>Methods: </strong>We carried out whole-genome sequencing of formalin-fixed paraffin-embedded (FFPE) samples of sinonasal adenocarcinomas from ten wood dust-exposed and six non-exposed individuals, with partial tobacco exposure data. Sequences were analyzed for the presence of mutational signatures matching COSMIC database signatures. Driver mutations and CN variant regions were characterized.</p><p><strong>Results: </strong>Mutation burden was higher in samples of wood dust-exposed patients (p = 0.016). Reactive oxygen species (ROS) damage-related mutational signatures were almost exclusively identified in ITAC subtype samples (p = 0.00055). Tobacco smoke mutational signatures were observed in samples of patients with tobacco exposure or missing information, but not in samples from non-exposed patients. A tetraploidy copy number (CN) signature was enriched in ITAC subtype (p = 0.042). CN variation included recurrent gains in COSMIC Cancer Gene Census genes TERT, SDHA, RAC1, ETV1, PCM1, and MYC. Pathogenic variants were observed most frequently in TP53, NF1, CHD2, BRAF, APC, and LRP1B. Driver mutations and copy number gains did not segregate by subtype.</p><p><strong>Conclusions: </strong>Our analysis identified distinct mutational characteristics in ITAC and non-ITAC. Mutational signature analysis may eventually become useful for documentation of occupation-related cancer, while the exact mechanisms behind wood dust-driven carcinogenesis remain elusive. The presence of homologous recombination deficiency signatures implies a novel opportunity for treatment, but further studies are needed.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"12"},"PeriodicalIF":1.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854487","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 spectrum of TP53 mutations in Rwandan patients with gastric cancer.","authors":"Augustin Nzitakera, Jean Bosco Surwumwe, Ella Larissa Ndoricyimpaye, Schifra Uwamungu, Delphine Uwamariya, Felix Manirakiza, Marie Claire Ndayisaba, Gervais Ntakirutimana, Benoit Seminega, Vincent Dusabejambo, Eric Rutaganda, Placide Kamali, François Ngabonziza, Rei Ishikawa, Belson Rugwizangoga, Yuji Iwashita, Hidetaka Yamada, Kimio Yoshimura, Haruhiko Sugimura, Kazuya Shinmura","doi":"10.1186/s41021-024-00302-y","DOIUrl":"10.1186/s41021-024-00302-y","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer.</p><p><strong>Results: </strong>Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon-intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed.</p><p><strong>Conclusions: </strong>Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"8"},"PeriodicalIF":1.7,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065126","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":"Lack of in vivo mutagenicity of carbendazim in the liver and glandular stomach of MutaMice.","authors":"Takako Iso, Kenichiro Suzuki, Yasumasa Murata, Nozomu Hirose, Takaaki Umano, Katsuyoshi Horibata, Kei-Ichi Sugiyama, Akihiko Hirose, Kenichi Masumura, Mariko Matsumoto","doi":"10.1186/s41021-024-00299-4","DOIUrl":"10.1186/s41021-024-00299-4","url":null,"abstract":"<p><strong>Background: </strong>Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo.</p><p><strong>Results: </strong>MutaMice were treated with carbendazim orally at doses of 0 (corn oil), 250, 500, and 1,000 mg/kg/day once a day for 28 days. A lacZ assay was used to determine the mutant frequency (MF) in the liver and glandular stomach of mice. MutaMice were administered up to the maximum dose recommended by the Organization for Economic Co-operation and Development Test Guidelines for Chemicals No. 488 (OECD TG488). The lacZ MFs in the liver and glandular stomach of carbendazim-treated animals were not significantly different from those in the negative control animals. In contrast, positive control animals exhibited a significant increase in MFs in both the liver and glandular stomach.</p><p><strong>Conclusions: </strong>Carbendazim is non-mutagenic in the liver and glandular stomach of MutaMice following oral treatment.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"7"},"PeriodicalIF":1.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912417","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}