Genes and Environment最新文献

{"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}

{"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/cm² 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}

{"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}

{"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}

{"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}

{"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}

{"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 + H₂O₂, 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}

{"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}

{"title":"Transcription factor 7-like 2 gene- smoking interaction on the risk of diabetic nephropathy in Chinese Han population.","authors":"Peng Xue,&nbsp;Haihong Cao,&nbsp;Zhimin Ma,&nbsp;Ying Zhou,&nbsp;Nian Wang","doi":"10.1186/s41021-021-00194-2","DOIUrl":"https://doi.org/10.1186/s41021-021-00194-2","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the relationship between transcription factor 7-like 2 (TCF7L2) gene polymorphism and diabetic nephropathy (DN) risk, as well as the effect of gene-environment interactions on DN risk in Chinese Han population.</p><p><strong>Methods: </strong>The Hardy-Weinberg equilibrium (HWE) and the relationship between TCF7L2 gene single nucleotide polymorphism (SNPs) and DN susceptibility were evaluated by SNPStats. The interaction among four SNPs and environmental factors were tested by generalized multifactor dimensionality reduction (GMDR). The consistency of cross validation, accuracy of test balance and sign test were calculated to evaluate the interaction of each selection. The logistic regression was used to test the interaction between rs7903146 and current smoking by stratified analysis.</p><p><strong>Results: </strong>Logistic regression analysis indicated that the DN risk of rs7903146-T allele carriers were obviously higher than that in CC genotype carriers (CT + TT versus CC), adjusted OR (95 %CI) = 1.64 (1.24-2.06). However, we also discovered that people with rs12255372, rs11196205 and rs290487 minor allele had non-significant difference risk of DN compared with people with major allele. The GMDR model found a significant two-locus model (p = 0.0100) including rs7903146 and current smoking, suggesting a potential gene-environment interaction between rs7903146 and current smoking. Compared with never smokers with rs7903146- CC genotype, current smokers with rs7903146- CT or TT genotype had the highest DN risk. After covariate adjustment, OR (95 %CI) was 2.15 (1.58-2.78).</p><p><strong>Conclusions: </strong>We found a significant relationship of rs7903146-T alleles, and the interaction between rs7903146-T and current smoking with increased DN risk.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"26"},"PeriodicalIF":1.7,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00194-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39044217","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":"New homozygous gpt delta transgenic rat strain improves an efficiency of the in vivo mutagenicity assay.","authors":"Kenichi Masumura,&nbsp;Tomoko Ando,&nbsp;Akiko Ukai,&nbsp;Sho Fujiwara,&nbsp;Shigeo Yokose,&nbsp;Xinyue You,&nbsp;Takayoshi Suzuki,&nbsp;Hiroyuki Hayashi,&nbsp;Takehiko Nohmi,&nbsp;Hisayoshi Takagi,&nbsp;Masamitsu Honma","doi":"10.1186/s41021-021-00195-1","DOIUrl":"https://doi.org/10.1186/s41021-021-00195-1","url":null,"abstract":"<p><strong>Background: </strong>Gene mutation assays in transgenic rodents are useful tools to investigate in vivo mutagenicity in a target tissue. Using a lambda EG10 transgene containing reporter genes, gpt delta transgenic mice and rats have been developed to detect point mutations and deletions. The transgene is integrated in the genome and can be rescued through an in vitro packaging reaction. However, the packaging efficiency is lower in gpt delta rats than in mice, because of the transgene in gpt delta rats being heterozygous and in low copy number. To improve the packaging efficiency, we herein describe a newly developed homozygous gpt delta rat strain.</p><p><strong>Results: </strong>The new gpt delta rat has a Wistar Hannover background and has been successfully maintained as homozygous for the transgene. The packaging efficiency in the liver was 4 to 8 times higher than that of existing heterozygous F344 gpt delta rats. The frequency of gpt point mutations significantly increased in the liver and bone marrow of N-nitroso-N-ethylurea (ENU)- and benzo[a]pyrene (BaP)-treated rats. Spi^- deletion frequencies significantly increased in the liver and bone marrow of BaP-treated rats but not in ENU-treated rats. Whole genome sequencing analysis identified ≥ 30 copies of lambda EG10 transgenes integrated in rat chromosome 1.</p><p><strong>Conclusions: </strong>The new homozygous gpt delta rat strain showed a higher packaging efficiency, and could be useful for in vivo gene mutation assays in rats.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"25"},"PeriodicalIF":1.7,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-021-00195-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39097829","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}