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The effect of aging on the repeated-dose liver micronucleus assay. 衰老对重复剂量肝微核试验的影响。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-09-09 DOI: 10.1186/s41021-021-00212-3
Miyuki Shigano, Hironao Takasawa, Shuichi Hamada
{"title":"The effect of aging on the repeated-dose liver micronucleus assay.","authors":"Miyuki Shigano,&nbsp;Hironao Takasawa,&nbsp;Shuichi Hamada","doi":"10.1186/s41021-021-00212-3","DOIUrl":"https://doi.org/10.1186/s41021-021-00212-3","url":null,"abstract":"<p><strong>Background: </strong>The liver micronucleus (MN) assay is an effective and important in vivo test for detecting genotoxic compounds. In particular, the repeated-dose liver MN (RDLMN) assay which greatly facilitates incorporation of the liver MN assay into the general toxicity study has been developed. Usefulness of the RDLMN assay was appraised highly in the 7th International Workshops on Genotoxicity Testing (2017 in Tokyo) in that sufficient numbers and types of chemicals were studied and easy integration into the general toxicity study is preferred from the 3R's point of view. However, it was pointed out that it is necessary to evaluate the effect of age at the start of 4-week repeated administration, since there are limited data, where only those of rats of 6 week of age at the start of administration are available. In this study, we conducted the 4-week RDLMN assay using rats of 6 and 8 weeks of age (at the start of administration) to investigate the effect of age on the liver MN inducibility. Clofibrate, a weak inducer of liver MN, was used in this study to detect the slight difference in the liver MN induction.</p><p><strong>Results: </strong>The liver MN induced by clofibrate was detected in both rats of 6 and 8 weeks of age at the start of administration. However, the liver MN induction was lower in rats of 8 weeks of age compared to rats of 6 weeks of age at the start of administration.</p><p><strong>Conclusion: </strong>These results suggest that the liver MN inducibility decreases with age. Therefore, we recommend the use of rats of 6 weeks of age at start of administration to reliably detect the liver MN induction in the RDLMN assay.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"37"},"PeriodicalIF":1.7,"publicationDate":"2021-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39401732","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}
引用次数: 2
High resolution melting analysis and detection of Leishmania resistance: the role of multi drug resistance 1 gene. 利什曼原虫耐药的高分辨率熔融分析与检测:多药耐药基因1的作用。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-08-11 DOI: 10.1186/s41021-021-00210-5
Maryam Fekri Soofi Abadi, Alireza Moradabadi, Reza Vahidi, Saeedeh Shojaeepour, Sara Rostami, Iman Rad, Shahriar Dabiri
{"title":"High resolution melting analysis and detection of Leishmania resistance: the role of multi drug resistance 1 gene.","authors":"Maryam Fekri Soofi Abadi,&nbsp;Alireza Moradabadi,&nbsp;Reza Vahidi,&nbsp;Saeedeh Shojaeepour,&nbsp;Sara Rostami,&nbsp;Iman Rad,&nbsp;Shahriar Dabiri","doi":"10.1186/s41021-021-00210-5","DOIUrl":"https://doi.org/10.1186/s41021-021-00210-5","url":null,"abstract":"<p><strong>Background: </strong>Pentavalent antimonial compounds are currently used to treat leishmaniasis and resistance to these drugs is a serious problem. Multidrug resistance protein is an efflux pump of the cell membrane that expels foreign compounds. This study designed to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene, in biopsy specimens of Leishmania tropica, with high resolution melting (HRM) method. In this experimental study, genomic DNA was extracted from 130 patients with skin leishmaniasis. Then, nucleotide changes were investigated throughout the gene using HRM and sequencing methods. The samples categorized in 5 groups by differences in the melting temperature (Tm).</p><p><strong>Result: </strong>The nucleotide changes analysis showed that 61% of the samples of different groups that were unresponsive to drug had mutations in the MDR1 gene, which were also confirmed by the sequencing method. These mutations can be one of the factors responsible for non-responsiveness to the treatment.</p><p><strong>Conclusion: </strong>According to the findings, it seems that mutation in MDR1 gene could be responsible for drug resistance to pentavalent antimonial compounds. Furthermore, HRM method can be used to diagnose drug resistance in leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in the leishmania affected patients.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"36"},"PeriodicalIF":1.7,"publicationDate":"2021-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39302035","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}
引用次数: 1
PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40. PRDX1对鸡DT40体内活性氧的生存和维持至关重要。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-08-05 DOI: 10.1186/s41021-021-00211-4
Takahito Moriwaki, Akari Yoshimura, Yuki Tamari, Hiroyuki Sasanuma, Shunichi Takeda, Masayuki Seki, Keizo Tano
{"title":"PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40.","authors":"Takahito Moriwaki,&nbsp;Akari Yoshimura,&nbsp;Yuki Tamari,&nbsp;Hiroyuki Sasanuma,&nbsp;Shunichi Takeda,&nbsp;Masayuki Seki,&nbsp;Keizo Tano","doi":"10.1186/s41021-021-00211-4","DOIUrl":"https://doi.org/10.1186/s41021-021-00211-4","url":null,"abstract":"<p><strong>Background: </strong>Peroxiredoxin 1 (PRDX1) is a member of a ubiquitous family of thiol peroxidases that catalyze the reduction of peroxides, including hydrogen peroxide. It functions as an antioxidant enzyme, similar to catalase and glutathione peroxidase. PRDX1 was recently shown act as a sensor of reactive oxygen species (ROS) and play a role in ROS-dependent intracellular signaling pathways. To investigate its physiological functions, PRDX1 was conditionally disrupted in chicken DT40 cells in the present study.</p><p><strong>Results: </strong>The depletion of PRDX1 resulted in cell death with increased levels of intracellular ROS. PRDX1-depleted cells did not show the accumulation of chromosomal breaks or sister chromatid exchange (SCE). These results suggest that cell death in PRDX1-depleted cells was not due to DNA damage. 2-Mercaptoethanol protected against cell death in PRDX1-depleted cells and also suppressed elevations in ROS.</p><p><strong>Conclusions: </strong>PRDX1 is essential in chicken DT40 cells and plays an important role in maintaining intracellular ROS homeostasis (or in the fine-tuning of cellular ROS levels). Cells deficient in PRDX1 may be used as an endogenously deregulated ROS model to elucidate the physiological roles of ROS in maintaining proper cell growth.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"35"},"PeriodicalIF":1.7,"publicationDate":"2021-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00211-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39278955","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}
引用次数: 4
miR221 regulates cell migration by targeting annexin a1 expression in human mesothelial MeT-5A cells neoplastic-like transformed by multi-walled carbon nanotube. miR221通过靶向多壁碳纳米管转化的人间皮MeT-5A细胞中膜联蛋白a1的表达调控细胞迁移。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-08-02 DOI: 10.1186/s41021-021-00209-y
Li Ju, Lijin Zhu, Hao Wu, Min Yu, Xianhong Yin, Zhenyu Jia, Lingfang Feng, Shibo Ying, Hailing Xia, Shuzhi Zhang, Jianlin Lou, Jun Yang
{"title":"miR221 regulates cell migration by targeting annexin a1 expression in human mesothelial MeT-5A cells neoplastic-like transformed by multi-walled carbon nanotube.","authors":"Li Ju,&nbsp;Lijin Zhu,&nbsp;Hao Wu,&nbsp;Min Yu,&nbsp;Xianhong Yin,&nbsp;Zhenyu Jia,&nbsp;Lingfang Feng,&nbsp;Shibo Ying,&nbsp;Hailing Xia,&nbsp;Shuzhi Zhang,&nbsp;Jianlin Lou,&nbsp;Jun Yang","doi":"10.1186/s41021-021-00209-y","DOIUrl":"https://doi.org/10.1186/s41021-021-00209-y","url":null,"abstract":"<p><strong>Background: </strong>Multi-walled carbon nanotube (MWCNT) is one of the most widely used manufactured nanomaterials, however, its potential harmful effect on human health is of great concern. Previously we have shown the acute and chronic exposure to MWCNT induced different responses in human mesothelial MeT-5A cells. In the current study, MeT-5A cells were continuously subjected to MWCNT exposure at 10 μg/cm<sup>2</sup> for 48 h per passage, up to a whole year, to further clarify the carcinogesis and its potential mechanisms of MWCNT.</p><p><strong>Results: </strong>After one-year MWCNT treatment, MeT-5A cells exhibited neoplastic-like properties, including morphological changes, anchorage-independent growth, increased cell proliferation and cell migration. Further examination revealed the expression of microRNA 221 (miR221) was gradually decreased, while the annexin a1 expression was increased at both the mRNA and protein level during the exposure. Bioinformatic analysis indicated that annexin a1 is a target for miR221 regulation, and it was confirmed by transfecting cells with miR221 mimics, which resulted in the downregulation of annexin a1. Detailed analyses demonstrated miR221 was involved in the regulation of cell migration, e.g., downregulation of miR221 or overexpression of ANNEXIN A1, contributed to the increased cell migration. In contrast, overexpression of miR221 or downregulation of ANNEXIN A1 slowed cell migration.</p><p><strong>Conclusions: </strong>Taken together, these results point to a neoplastic-transforming property of MWCNT, and the miR221-annexin a1 axis is involved in the regulation of cell migration in the transformed cells.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"34"},"PeriodicalIF":1.7,"publicationDate":"2021-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00209-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39269420","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}
引用次数: 2
Dietary heterocyclic aromatic amine intake and cancer risk: epidemiological evidence from Japanese studies. 饮食中杂环芳香胺的摄入与癌症风险:来自日本研究的流行病学证据。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-07-27 DOI: 10.1186/s41021-021-00202-5
Motoki Iwasaki, Shoichiro Tsugane
{"title":"Dietary heterocyclic aromatic amine intake and cancer risk: epidemiological evidence from Japanese studies.","authors":"Motoki Iwasaki,&nbsp;Shoichiro Tsugane","doi":"10.1186/s41021-021-00202-5","DOIUrl":"https://doi.org/10.1186/s41021-021-00202-5","url":null,"abstract":"<p><p>Heterocyclic aromatic amines (HAAs), which are formed from the reaction of creatine or creatinine, amino acids, and sugars in meat and fish cooked at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models. Following advances in the dietary assessment of HAA intake in epidemiological studies - including development of a validated meat-cooking module and a specialized food composition database - a number of epidemiological studies have specifically examined the association of HAA intake and cancer risk, most of which were conducted in Western countries. Given that dietary habits and cooking methods differ across countries, however, epidemiological investigation of dietary HAA intake requires a population-specific assessment method. Here, we developed a practical method for assessing dietary HAA intake among Japanese using a food frequency questionnaire (FFQ) and evaluated its validity for use in epidemiological studies by comparison with 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) levels in human hair. The Japan Public Health Center-based Prospective Study reported that daily intake of HAAs among Japanese was relatively low, and that more than 50% of total intake in mainland Japan was derived from fish. Only four case-control studies in Japan have been reported so far, for colorectal, stomach and prostate cancer, and colorectal adenoma. A statistically significant positive association was found between 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ) and the risk of colorectal adenoma and between individual and total HAAs and the risk of prostate cancer. In contrast, no association was observed for colorectal or stomach cancer, or for colorectal adenoma among men. We also found that the limited and inconsistent findings among epidemiological studies are due to the difficulty in assessing exposure levels of HAAs. In addition to further evidence from prospective cohort studies in Japanese based on dietary HAA intake estimated by FFQs, studies using other methods to assess HAA exposure, such as biomarkers, are highly anticipated.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"33"},"PeriodicalIF":1.7,"publicationDate":"2021-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00202-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39227432","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}
引用次数: 5
Achievements and memories of Dr. Takashi Sugimura. 杉村隆博士的成就与回忆。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-07-20 DOI: 10.1186/s41021-021-00203-4
Keiji Wakabayashi
{"title":"Achievements and memories of Dr. Takashi Sugimura.","authors":"Keiji Wakabayashi","doi":"10.1186/s41021-021-00203-4","DOIUrl":"https://doi.org/10.1186/s41021-021-00203-4","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"31"},"PeriodicalIF":1.7,"publicationDate":"2021-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00203-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39203589","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}
引用次数: 0
Gene expression analysis in NSAID-induced rat small intestinal disease model with the intervention of berberine by the liquid chip technology. 用液体芯片技术分析小檗碱干预非甾体抗炎药诱导的大鼠小肠疾病模型的基因表达。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-07-20 DOI: 10.1186/s41021-021-00205-2
Guanqun Chao, Qianqian Wang, Fangxu Ye, Shuo Zhang
{"title":"Gene expression analysis in NSAID-induced rat small intestinal disease model with the intervention of berberine by the liquid chip technology.","authors":"Guanqun Chao,&nbsp;Qianqian Wang,&nbsp;Fangxu Ye,&nbsp;Shuo Zhang","doi":"10.1186/s41021-021-00205-2","DOIUrl":"https://doi.org/10.1186/s41021-021-00205-2","url":null,"abstract":"<p><strong>Objective: </strong>Investigate the effect and mechanism of berberine on the small intestinal mucosa of non-steroidal anti-inflammatory drugs (NSAIDs) related small intestinal injury.</p><p><strong>Materials and methods: </strong>Twenty-four SD rats were randomly divided into control group, model group and intervention group. The model group and intervention group were treated with diclofenac (7.5 mg/kg·d, 2/d), a total of 4 days tube feeding, and the intervention group was treated with 50 mg/kg·d intragastric administration of berberine after 2 days. The control group was treated with 7.5 mg/kg·d, 2/d 0.9% saline tube feeding. Then we screened differential expression of colonic mucosal gene by the liquid chip technology.</p><p><strong>Results: </strong>Compared with the control group, macroscopic and histology score of the model group increased significantly (P < 0.05), HTR4, HTR1a, F2RL3, CALCA, NPY, CRHR2, IL1b, P2RX3, TPH1, HMOX1, TRPV1, VIP, F2RL1, SLC6A4, TFF2, AQP8 content were significantly increased (P < 0.05), NOS1 content decreased significantly (P < 0.05); Compared with the model group, macroscopic and histology score of the intervention group improved significantly (P < 0.05), and HTR4, F2RL3, NPY, CRHR2, IL1b, VIP, AQP8 content were significantly lower (P < 0.05), NOS1 content increased significantly (P < 0.05).</p><p><strong>Conclusion: </strong>Berberine has a protective effect on NSAID-associated small intestinal injury, the mechanism may be that berberine decreases the expression of intestinal mucosa HTR4, F2RL3, NPY, CRHR2, IL1b, VIP, AQP8, and increases the expression of NOS1, that to reduce intestinal permeability and protect intestinal mucosal barrier.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"32"},"PeriodicalIF":1.7,"publicationDate":"2021-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00205-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39203591","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}
引用次数: 0
Metabolism and biomarkers of heterocyclic aromatic amines in humans. 人体内杂环芳香胺的代谢和生物标志物。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-07-16 DOI: 10.1186/s41021-021-00200-7
Medjda Bellamri, Scott J Walmsley, Robert J Turesky
{"title":"Metabolism and biomarkers of heterocyclic aromatic amines in humans.","authors":"Medjda Bellamri,&nbsp;Scott J Walmsley,&nbsp;Robert J Turesky","doi":"10.1186/s41021-021-00200-7","DOIUrl":"https://doi.org/10.1186/s41021-021-00200-7","url":null,"abstract":"<p><p>Heterocyclic aromatic amines (HAAs) form during the high-temperature cooking of meats, poultry, and fish. Some HAAs also arise during the combustion of tobacco. HAAs are multisite carcinogens in rodents, inducing cancer of the liver, gastrointestinal tract, pancreas, mammary, and prostate glands. HAAs undergo metabolic activation by N-hydroxylation of the exocyclic amine groups to produce the proposed reactive intermediate, the heteroaryl nitrenium ion, which is the critical metabolite implicated in DNA damage and genotoxicity. Humans efficiently convert HAAs to these reactive intermediates, resulting in HAA protein and DNA adduct formation. Some epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and elevated cancer risk of the colorectum, pancreas, and prostate. However, other studies have reported no associations between cooked meat and these cancer sites. A significant limitation in epidemiology studies assessing the role of HAAs and cooked meat in cancer risk is their reliance on food frequency questionnaires (FFQ) to gauge HAA exposure. FFQs are problematic because of limitations in self-reported dietary history accuracy, and estimating HAA intake formed in cooked meats at the parts-per-billion level is challenging. There is a critical need to establish long-lived biomarkers of HAAs for implementation in molecular epidemiology studies designed to assess the role of HAAs in health risk. This review article highlights the mechanisms of HAA formation, mutagenesis and carcinogenesis, the metabolism of several prominent HAAs, and the impact of critical xenobiotic-metabolizing enzymes on biological effects. The analytical approaches that have successfully biomonitored HAAs and their biomarkers for molecular epidemiology studies are presented.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"29"},"PeriodicalIF":1.7,"publicationDate":"2021-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39192335","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}
引用次数: 12
Free radical-mediated acetaldehyde formation by model reactions of dietary components: effects of meat, wine, cooking oil and coffee. 膳食成分模型反应中自由基介导的乙醛形成:肉、酒、食用油和咖啡的影响。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-07-09 DOI: 10.1186/s41021-021-00201-6
Hiroshi Kasai, Kazuaki Kawai
{"title":"Free radical-mediated acetaldehyde formation by model reactions of dietary components: effects of meat, wine, cooking oil and coffee.","authors":"Hiroshi Kasai,&nbsp;Kazuaki Kawai","doi":"10.1186/s41021-021-00201-6","DOIUrl":"https://doi.org/10.1186/s41021-021-00201-6","url":null,"abstract":"<p><strong>Background: </strong>Alcohol consumption and the ingestion of red meat and oxidized cooking oil are risk factors of gastric and colorectal cancers. We reported that acetaldehyde (AcAld) is generated from Heme/Mb/Meat-Linoleate-EtOH model reaction mixtures, and thus could be a new plausible mechanism for the carcinogenesis (Kasai and Kawai, ACS Omega, 2021).</p><p><strong>Results: </strong>In this study, we investigated the effects of wine and coffee, in addition to meat components, on this reaction. Depending on the conditions, such as pH, reaction time and choice of free hemin, myoglobin (Mb), as well as meat extracts (raw meat, baked meat, salami), wine and coffee enhanced AcAld formation. Polyphenols in red wine and coffee may stimulate AcAld formation by acting as pro-oxidants in the presence of Heme/Mb/Meat. In a model reaction of Mb + EtOH + H<sub>2</sub>O<sub>2</sub>, we observed time-dependent AcAld formation. In support of these in vitro data, after the consumption of a red meat-rich diet with red wine, the fecal AcAld level significantly increased as compared to the levels associated with a diet of fish + wine, or red meat without alcohol.</p><p><strong>Conclusions: </strong>These results suggested that AcAld generation from dietary components may be an important mechanism of gastrointestinal tract carcinogenesis.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"28"},"PeriodicalIF":1.7,"publicationDate":"2021-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00201-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39169970","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}
引用次数: 1
Characteristic mutations induced in the small intestine of Msh2-knockout gpt delta mice. msh2敲除gpt δ小鼠小肠中诱导的特征性突变。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2021-07-05 DOI: 10.1186/s41021-021-00196-0
Yasunobu Aoki, Mizuki Ohno, Michiyo Matsumoto, Michi Matsumoto, Kenichi Masumura, Takehiko Nohmi, Teruhisa Tsuzuki
{"title":"Characteristic mutations induced in the small intestine of Msh2-knockout gpt delta mice.","authors":"Yasunobu Aoki,&nbsp;Mizuki Ohno,&nbsp;Michiyo Matsumoto,&nbsp;Michi Matsumoto,&nbsp;Kenichi Masumura,&nbsp;Takehiko Nohmi,&nbsp;Teruhisa Tsuzuki","doi":"10.1186/s41021-021-00196-0","DOIUrl":"https://doi.org/10.1186/s41021-021-00196-0","url":null,"abstract":"<p><strong>Background: </strong>Base pair mismatches in genomic DNA can result in mutagenesis, and consequently in tumorigenesis. To investigate how mismatch repair deficiency increases mutagenicity under oxidative stress, we examined the type and frequency of mutations arising in the mucosa of the small intestine of mice carrying a reporter gene encoding guanine phosphoribosyltransferase (gpt) and in which the Msh2 gene, which encodes a component of the mismatch repair system, was either intact (Msh2+/+::gpt/0; Msh2-bearing) or homozygously knockout (KO) (Msh2-/-::gpt/0; Msh2-KO).</p><p><strong>Results: </strong>Gpt mutant frequency in the small intestine of Msh2-KO mice was about 10 times that in Msh2-bearing mice. Mutant frequency in the Msh2-KO mice was not further enhanced by administration of potassium bromate, an oxidative stress inducer, in the drinking water at a dose of 1.5 g/L for 28 days. Mutation analysis showed that the characteristic mutation in the small intestine of the Msh2-KO mice was G-to-A transition, irrespective of whether potassium bromate was administered. Furthermore, administration of potassium bromate induced mutations at specific sites in gpt in the Msh2-KO mice: G-to-A transition was frequently induced at two known sites of spontaneous mutation (nucleotides 110 and 115, CpG sites) and at nucleotides 92 and 113 (3'-side of 5'-GpG-3'), and these sites were confirmed to be mutation hotspots in potassium bromate-administered Msh2-KO mice. Administration of potassium bromate also induced characteristic mutations, mainly single-base deletion and insertion of an adenine residue, in sequences of three to five adenine nucleotides (A-runs) in Msh2-KO mice, and elevated the overall proportion of single-base deletions plus insertions in Msh2-KO mice.</p><p><strong>Conclusions: </strong>Our previous study revealed that administration of potassium bromate enhanced tumorigenesis in the small intestine of Msh2-KO mice and induced G-to-A transition in the Ctnnb1 gene. Based on our present and previous observations, we propose that oxidative stress under conditions of mismatch repair deficiency accelerates the induction of single-adenine deletions at specific sites in oncogenes, which enhances tumorigenesis in a synergistic manner with G-to-A transition in other oncogenes (e.g., Ctnnb1).</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"27"},"PeriodicalIF":1.7,"publicationDate":"2021-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00196-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39085344","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}
引用次数: 1
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