Genes and Environment最新文献

{"title":"In vivo and in vitro genotoxicity of N-nitrosopyrrolidine following UVA irradiation.","authors":"Yusuke Hanaki, Sakae Arimoto-Kobayashi","doi":"10.1186/s41021-025-00334-y","DOIUrl":"10.1186/s41021-025-00334-y","url":null,"abstract":"<p><p>N-nitrosopyrrolidine (NPYR) is a volatile nitrosamine that is thought to be a human carcinogen. It is found in air, wastewater, food, and feed. Photo-activation of NPYR can occur as it drifts through the environment. We previously found that NPYR irradiated in phosphate buffer was directly mutagenic without metabolic activation or simultaneous irradiation. Here, we aimed to determine NPYR activity after UVA irradiation. The mutagenic activity of irradiated NPYR was relatively stable, and ~ 23% of it persisted after 168 h of storage at 37 °C. Micronuclei (MN) were also found without metabolic activation in human-derived keratinocytes (HaCaT cells) after NPYR irradiation in vitro and the peripheral blood reticulocytes (PBRs) of mice with inhibited cytochrome-P450-mediated metabolism then injected with irradiated NPYR in vivo. The active photoproduct of NPYR is thought to be genotoxic to bone marrow, resulting in MN formation in PBRs. The action spectrum of MN formation in PBRs exposed to NPYR irradiated with monochromatic light was plotted along the absorption curve. The production ratio of active NPYR photoproduct followed the NPYR absorption curve. Genotoxicity becomes systemic with externally irradiated NPYR that penetrates the skin or when NPYR is irradiated just under the skin and enters the systemic circulation. Risk analyses of public health-related volatile N-nitrosamines generated via environmental photoactivation including NPYR, should be considered.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"11"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150269","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":"Genes and Environment: reflections on its journey, past and future.","authors":"Takashi Yagi","doi":"10.1186/s41021-025-00333-z","DOIUrl":"10.1186/s41021-025-00333-z","url":null,"abstract":"<p><p>This article outlines the history and development of Genes and Environment, the official journal of the Japanese Environmental Mutagen and Genome Society (JEMS). In the 1970s, there was growing concern about the mutagenicity of chemical substances, leading to the establishment of JEMS. The society began publishing its journal, Environmental Mutagen Research, and renamed Genes and Environment in 2006 to focus on gene-environment interactions and promote international collaboration. The journal transitioned to free-access and started publishing in English to expand its reach globally.From 2012, the journal partnered with BioMed Central (BMC) to become an open-access publication, leading to its inclusion in Scopus, PubMed, and SCIE, and an improvement in its CiteScore and Impact Factor. JEMS also sought funding from Japan's Grants-in-Aid for Scientific Research (KAKENHI) to support international dissemination of research.Despite progress, challenges remain, such as limited submissions from certain regions and a need for greater global recognition. To further internationalize JEMS, efforts are being made to elevate the quality of research and broaden membership diversity, with a focus on making JEMS' activities and publications more accessible to the global scientific community.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"10"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119591","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":"Report of the 47th annual conference and the golden jubilee year meeting of the Environmental Mutagen Society of India (EMSI) and international conference on environmental and molecular mutagenesis: genomic integrity and implication to human health, Tamil Nadu, India, January 29-31, 2025.","authors":"Bani Bandana Ganguly","doi":"10.1186/s41021-025-00331-1","DOIUrl":"https://doi.org/10.1186/s41021-025-00331-1","url":null,"abstract":"<p><p>The 47th Annual Conference and the Golden Jubilee Year Meeting of the Environmental Mutagen Society of India (EMSI) and International Conference on Environmental and Molecular Mutagenesis: Genomic Integrity and Implication to Human Health was held at the Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, India, during January 29-31, 2025. Among the 18 international speakers, the former president of The Japanese Environmental Mutagen and Genome Society, the former and present presidents of UK Environmental Mutagen Societies (EMS) and the Office Bearers of the Indian EMS participated in the conference. The pre-conference workshop was held at the same venue one day before the main conference. Plenary and invited lecturers spoke about the assay systems, study parameters, biomarkers of disease onset, regulatory issues, and technological advancements in mutagenicity and carcinogenicity research. In brief: the effects of pesticides, heavy metals, nanoparticles, pharmaceutical impurities, UV-radiation, etc. on DNA damage and alterations in signalling and metabolic pathways were discussed. Discussion on errors in DNA-repair leading to disease-onset, remediation of genotoxicity with phytochemicals, identification of drug candidates, and progress in technological advancements such as error corrected Next Generation Sequencing (ecNGS) justified the theme of the Mutagen Societies. Altogether, 12 plenaries, 37 invited lectures, and general presentations, including 42 oral and 80 posters made the conference a grand success through lively interactive discussions. The organising team and EMSI expressed sincere thanks and gratitude to all the participants.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"9"},"PeriodicalIF":2.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013132","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":"Formation of the toxic furan metabolite 2-butene-1,4-dial through hemin-induced degradation of 2,4-alkadienals in fried foods.","authors":"Hiroshi Kasai, Kazuaki Kawai, Koichi Fujisawa","doi":"10.1186/s41021-025-00330-2","DOIUrl":"10.1186/s41021-025-00330-2","url":null,"abstract":"<p><strong>Background: </strong>The mechanism of protein modification by 2,4-alkadienals (ADE), lipid peroxidation products prevalent in fried foods, was investigated through model reactions.</p><p><strong>Results: </strong>A mixture of 2,4-heptadienal (HDE) and hemin was initially incubated at pH 3.0-7.4, followed by treatment with acetyl-cysteine (AcCys) and acetyl-lysine (AcLys) at pH 7.4. Analysis via HPLC revealed a product with a characteristic UV spectrum as the primary peak. This product was identified as an AcCys-pyrrole-AcLys (CPL) crosslink derived from AcCys, 2-butene-1,4-dial (BDA), and AcLys. Increasing the HDE concentration in the initial reaction led to maximum CPL formation at pH 3.5 in the presence of hemin. Lowering the HDE concentration with a higher Cys/HDE ratio resulted in CPL formation, which was observed at pH 7.4 and 3.5 in the presence of hemin. Upon incubation of ADE and hemin at pH 3.0-3.5, BDA was directly identified as 2,4-dinitrophenylhydrazone. BDA was also detected in the 2,4-decadienal reaction mixture. Additionally, a notable propensity for high BDA-dC adduct formation with hemin under acidic conditions was observed, consistent with the results of CPL assay and BDA-2,4-dinitrophenylhydrazone analysis.</p><p><strong>Conclusions: </strong>1) BDA is efficiently generated from ADE in the presence of hemin under gastric conditions, and 2) BDA-derived CPL can also form under physiological conditions (pH 7.4) through the interaction of ADE, hemin, Cys, and Lys. BDA is recognized as the primary reactive metabolite of the suspected carcinogen furan (IARC, 2B). Given that human intake of ADE exceeds that of furan and acrylamide (IARC 2A) by several orders of magnitude, and the estimated hemin concentration in the stomach post-meal is comparable to the present study, a substantial amount of BDA may form in the stomach following consumption of fried foods and meat. The risk assessment of ADE warrants a thorough re-evaluation, based on the toxicity mechanism of BDA.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"8"},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811032","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":"Role of TDP2 in the repair of DNA damage induced by the radiomimetic drug Bleomycin.","authors":"Naoto Shimizu, Kazuki Izawa, Mubasshir Washif, Ryosuke Morozumi, Kouji Hirota, Masataka Tsuda","doi":"10.1186/s41021-025-00329-9","DOIUrl":"https://doi.org/10.1186/s41021-025-00329-9","url":null,"abstract":"<p><strong>Background: </strong>Bleomycin (Bleo) is a glycopeptide with potent antitumor activity that induces DNA double-strand breaks (DSBs) through free radical generation, similar to ionizing radiation (IR). Therefore, Bleo is considered a radiomimetic drug. However, differences in DNA repair mechanisms between IR- and Bleo-induced DNA damage have not been fully elucidated. Therefore, in the present study, we examined a panel of repair-deficient human TK6 cell lines to elucidate the relative contributions of individual repair factors.</p><p><strong>Results: </strong>Our comprehensive profiling indicated that both non-homologous end joining (NHEJ) and homologous recombination (HR) contributed to DSB repair induced by X-rays and Bleo. Furthermore, tyrosyl-DNA phosphodiesterase (TDP)-related repair was a significant factor for cellular sensitivity to Bleo treatment. TDP1^-/-/TDP2^-/- cells exhibited greater sensitivity to Bleo than TDP1^-/- or TDP2^-/- cells, but not to X-rays. In addition, we determined whether TDP2 is involved in the repair of Bleo-induced DSBs using a neutral comet assay. In TDP1-deficient cells, knockout of TDP2 resulted in a significant delay in the repair kinetics of DSBs induced by Bleo, but not by X-rays.</p><p><strong>Conclusions: </strong>The contribution of the TDP-related pathway to DSB repair significantly differed between IR and radiomimetic drugs. The discovery of this novel TDP2-dependent repair of DSBs resulting from radiomimetic drug exposure indicates that TDP1 and TDP2 inhibition in combination with radiomimetic drugs represents a strategy for cancer treatment.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"7"},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742782","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 new era shaped by environmental genome monitoring - symposium of the japanese environmental mutagen and genome society (JEMS), 2024.","authors":"Hiroshi Honda, Takayoshi Suzuki, Masaaki Kitajima, Natsuko Ito Kondo, Kaede Miyata, Shunsuke Utsumi, Masami Yamada","doi":"10.1186/s41021-025-00327-x","DOIUrl":"10.1186/s41021-025-00327-x","url":null,"abstract":"<p><p>The symposium \"The New Era Shaped by Environmental Genome Monitoring,\" held in December 2024 by the Japanese Environmental Mutagen and Genome Society (JEMS), aimed to explore the interdisciplinary collaborations that are essential for the development of new scopes in environmental genome monitoring. This event highlighted the necessity of integrating mutagenicity research with ecological assessments to enhance public health and biodiversity conservation. Presentations focused on the evolving landscape of environmental genomics, including metagenomic analyses for antibiotic resistance, viral genomic surveillance in wastewater, and innovations in noninvasive biodiversity and stress monitoring through environmental DNA and RNA. This report summarizes the key discussions and presentations from the symposium, underscoring the critical role of environmental genome monitoring in shaping future safety research.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"6"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648318","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":"Environmental factors in gastric carcinogenesis and preventive intervention strategies.","authors":"Yuzhi Tan, Juntaro Matsuzaki, Yoshimasa Saito, Hidekazu Suzuki","doi":"10.1186/s41021-025-00328-w","DOIUrl":"10.1186/s41021-025-00328-w","url":null,"abstract":"<p><p>Gastric cancer, a significant global health concern, arises from a complex interplay of genetic and environmental factors. Helicobacter pylori (H. pylori) infection is a major risk factor that can be mitigated through eradication strategies. Epstein-Barr virus (EBV) infection causes a distinct subtype of gastric cancer called EBV-associated gastric cancer. The gastric microbiome, a dynamic ecosystem, is also involved in carcinogenesis, particularly dysbiosis and specific bacterial species such as Streptococcus anginosus. Long-term use of proton pump inhibitors and potassium-competitive acid blockers also increases the risk of gastric cancer, whereas non-steroidal anti-inflammatory drugs including aspirin may have a protective effect. Smoking significantly increases the risk, and cessation can reduce it. Dietary factors such as high intake of salt, processed meats, and red meat may increase the risk, whereas a diet rich in fruits and vegetables may be protective. Extracellular vesicles, which are small membrane-bound structures released by cells, modulate the tumor microenvironment and may serve as biomarkers for risk stratification and as therapeutic targets in gastric cancer. This review highlights the multifaceted etiology of gastric cancer and its risk factors and emphasizes the importance of a multi-pronged approach to prevention including H. pylori eradication and modification of lifestyle factors, as well as the potential of microbiome-based and EV-based interventions. Further research is needed to refine risk stratification and to develop personalized prevention strategies.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"5"},"PeriodicalIF":2.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566914","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":"Cancer prevention: past challenges and future directions.","authors":"HeeKyung Seong, Runa Izutsu, Mitsuhiko Osaki, Futoshi Okada","doi":"10.1186/s41021-025-00326-y","DOIUrl":"10.1186/s41021-025-00326-y","url":null,"abstract":"<p><p>Almost 70 years have passed since the molecular mechanism of carcinogenesis was hypothesized to involve multiple gene mutations. More than 1,000 cancer-related genes, including oncogenes and tumor suppressor genes, accelerate carcinogenesis by altering molecular functions and gene expression through mutations and epigenetic changes and have been shown to cause multistep carcinogenesis in several organ cancers. The elucidation of cancer-related gene abnormalities has led to the development of molecular-targeted therapies that focus on driver molecules, known as precision medicine, in addition to conventional treatments such as surgery, radiotherapy, and chemotherapy. Now that the mechanism of cancer development has been largely elucidated, options for cancer treatment and its outcomes have improved, and cancer research is moving to the next stage: cancer prevention. Cancer prevention using chemicals was first proposed approximately 50 years ago. It is the concept of stabilizing, arresting, or reverting precancerous lesions to normal tissues using synthetic vitamin A analogs (retinoids). Cancer chemoprevention is now considered to consist of three elements: \"primary prevention,\" which prevents the development of tumors and prevents benign tumors converting into more malignant ones; \"secondary prevention,\" which aims for early detection through cancer screening and treatment; and \"tertiary prevention,\" which reduces the risk of recurrence and extends the time until death from cancer through treatment. Consequently, there is no clear boundary between the prevention and treatment strategies. Therefore, chemoprevention targets the entire process, from normal cells to precancerous lesions, malignant progression of tumors, and death by cancer. Basic and clinical research has revealed that cancer prevention is influenced by race, regional, and national differences, as well as individual differences such as genetic factors, environmental factors, and lifestyle habits. This review provides an overview of the progress made in cancer prevention and summarizes future directions.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"4"},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515268","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":"History of the Organisation for Economic Co-operation and Development (OECD) test guidelines for non-animal test methods in Japan.","authors":"Hajime Kojima","doi":"10.1186/s41021-024-00323-7","DOIUrl":"10.1186/s41021-024-00323-7","url":null,"abstract":"<p><p>The number of alternatives to animal tests (non-animal test methods) for human health developed globally account for more than 40% of the test methods in the Organisation for Economic Co-operation and Development (OECD) Guidelines for the Testing of Chemicals (TGs). Within the TGs, the National Institute of Health Sciences (NIHS) has standardized 16 OECD TGs for human health, implemented four major revisions, and developed one test method for the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) S10 guidelines on photosafety. This review describes trends in the OECD and Japan that mainly focus on international standardizations of non-animal test methods for human health. Drawing from this experience, I hope Japan will advance new approach methodologies for detecting systemic toxicity, which are in global demand.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"3"},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065244","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":"Increased matrix metalloproteinase-1 expression by coexposure to UVA and cigarette sidestream smoke and contribution of histone acetylation.","authors":"Ryoma Ito, Yukako Komaki, Yuko Ibuki","doi":"10.1186/s41021-025-00325-z","DOIUrl":"10.1186/s41021-025-00325-z","url":null,"abstract":"<p><strong>Background: </strong>Skin is exposed to various environmental factors throughout life, and some of these factors are known to contribute to skin aging. Long-term solar UV exposure is a well-known cause of skin aging, as is cigarette smoke, which contains a number of chemicals. In this study, combined effect of UVA and cigarette sidestream smoke (CSS) on matrix metalloproteinase-1 (MMP-1) induction was investigated. MMP-1 is the main protease that initiates collagen type I fiber fragmentation in human skin and is associated with aging.</p><p><strong>Results: </strong>Combined exposure to UVA and CSS enhanced MMP-1 induction, accompanied by collagen type I (COL1A1) gene suppression. The basal expression of MMP-1 was higher in senescent cells than in normal cells, with a pronounced increase after coexposure to UVA and CSS. UVA irradiation resulted in global histone H3 acetylation, and we considered this was responsible for the MMP-1 upregulation. Histone deacetylase inhibitors, sodium acetate, propionate, and butyrate, all enhanced the CSS-induced MMP-1 according to the degree of histone acetylation.</p><p><strong>Conclusion: </strong>These results suggest that UVA and CSS additively induce MMP-1, which may lead to skin aging, and that such combined effect may further promote aging in aged skin. UVA-induced histone acetylation may contribute to MMP-1 induction.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"47 1","pages":"2"},"PeriodicalIF":2.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046384","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}