Journal of Environmental Pathology Toxicology and Oncology最新文献

{"title":"Adverse Effects of COVID-19 Treatments: A Special Focus on Susceptible Populations.","authors":"Beyza Nur Küçük,&nbsp;Rahime Şimşek,&nbsp;Selinay Başak Erdemli Köse,&nbsp;Anil Yirun,&nbsp;Pinar Erkekoglu","doi":"10.1615/JEnvironPatholToxicolOncol.2022039271","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2022039271","url":null,"abstract":"<p><p>On December 2019, the world faced a new pandemic caused by a novel type of coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is named as \"coronavirus disease 2019 (COVID-19).\" This RNA virus infected millions of people around the world causing millions of deaths. It takes approximately 8-10 years to develop a new drug and it seems hard to have a specific pharmaceutical agent against COVID-19. So far, there is only one drug that has applied for registration. The drugs used in clinics against COVID-19 were approved for malaria, human immunodeficiency syndrome (HIV), influenza A and B, and other viral diseases. All these drugs for COVID-19 treatment are being applied according to \"drug repurposing (drug repositioning)\" strategy. However, they could cause some severe adverse effects on susceptible populations. In some cases, patients can survive after disease. However, the adverse effects of these drugs may lead to morbidity and mortality later. In this review, drugs used against COVID-19 in clinics, their mechanisms of action and possible adverse effects on susceptible populations will be discussed.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"41 3","pages":"45-64"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40631203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-1246 Promotes Laryngeal Squamous Cell Carcinoma Progression by Interacting with THBS1.","authors":"Lifeng Wu,&nbsp;Na Zuo,&nbsp;Shuo Pan,&nbsp;Yue Wang,&nbsp;Qixue Wang,&nbsp;Jun Ma","doi":"10.1615/JEnvironPatholToxicolOncol.2022040516","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2022040516","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have been confirmed to be related to the occurrence and progress of multiple cancers, including laryngeal squamous cell carcinoma (LSCC). The present work focused on exploring the role of miR-1246 in LSCC and investigating the possible mechanisms. miR-1246 expression levels within clinical LSCC tissues and cell lines (TU212 and AMC-HN-8) were detected through quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Then the overall survival (OS) rates of LSCC patients with different miR-1246 expressions were assessed by the Kaplan-Meier method. In addition, the roles of miR-1246 in the proliferation, apoptosis and migration of TU212 and AMC-HN-8 cells were measured by colony formation, flow cytometry, wound-healing, and Western blot (WB) assays, respectively. Moreover, TargetScan was carried out to predict the miR-1246 targets (thrombospondin-1, THBS1), further confirmed by a dual-luciferase reporter assay. Afterward, the negative relationship between miR-1246 and THBS1 was assessed by qRT-PCR and WB. Furthermore, the restoring effects of THBS1 on TU212 and AMC-HN-8 functional roles transfected with miR-1246 inhibitor were further investigated. miR-1246 expression levels were increased in clinical LSCC tissues and cell lines. Patients with low miR-1246 expression exhibited improved OS rates. In addition, miR-1246 down-regulation notably suppressed cell proliferation and migration and induced cell apoptosis of TU212 and AMC-HN-8 cells. Moreover, THBS1 was predicted and confirmed as a direct target of miR-1246 and negatively related to miR-1246 expression. Mechanically, THBS1 inhibition partially rescued the effects of the miR-1246 inhibitor on proliferation, apoptosis and migration of TU212 and AMC-HN-8 cells. This study provides an experimental basis suggesting the potential of miR-1246/THBS1 as the novel markers for LSCC.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"41 3","pages":"65-75"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40631204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic Role of Heterogeneous Nuclear Ribonucleoprotein C in Multiple Cancer Types, with a Particular Focus on Lung Adenocarcinoma, Using a Pan-Cancer Analysis and Cell Line Experiments.","authors":"Libin Zhang,&nbsp;Hao Peng,&nbsp;Lihong Jiang","doi":"10.1615/JEnvironPatholToxicolOncol.2022042822","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2022042822","url":null,"abstract":"<p><p>Although some evidence has validated the connection between heterogeneous nuclear ribonucleoprotein C (HNRNPC) and the progression of tumors, a pan-cancer investigation is still required. Thus, we explored the oncogenic effect of HNRNPC across many tumors using The Cancer Genome Atlas datasets. Moreover, short hairpin RNAs (shRNAs) were found to repress HNRNPC in lung adenocarcinoma (LUAD) cells, and the effect on LUAD cells proliferation and metastasis was examined using a Cell Counting Kit-8, transwell, and invasion test. HNRNPC was found to be overexpressed in most cancers, and a divergent relationship was observed between the abnormal levels of HNRNPC and tumor prognosis. HNRNPC level was observed to correlate with the cancer-associated fibroblast infiltration, such as lung cancer. Furthermore, higher HNRNPC levels were found in LUAD tissues and cells. Subsequently, Kaplan-Meier analysis revealed that the increased HNRNPC level was connected with worse overall survival and disease-free survival in LUAD patients. Moreover, HNRNPC silencing reduced the progression of A549 and H1299 cells, including proliferation, migration, and invasion. This is the first pan-cancer investigation that presents a relatively systematic finding of the oncogenic effect of HNRNPC among many cancer types. Our data indicate that HNRNPC facilitates the biological processes of LUAD cells; nevertheless, further research on the mechanism underlying the role of HNRNPC in LUAD development is warranted.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"41 3","pages":"77-93"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40631205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PI3K/Akt/mTOR Pathways Inhibitors with Potential Prospects in Non-Small-Cell Lung Cancer.","authors":"Khalid Saad Alharbi,&nbsp;Mohammad Arshad Javed Shaikh,&nbsp;Waleed Hassan Almalki,&nbsp;Imran Kazmi,&nbsp;Fahad A Al-Abbasi,&nbsp;Sami I Alzarea,&nbsp;Syed Sarim Imam,&nbsp;Sultan Alshehri,&nbsp;Mohammed M Ghoneim,&nbsp;Sachin Kumar Singh,&nbsp;Dinesh Kumar Chellappan,&nbsp;Brian G Oliver,&nbsp;Kamal Dua,&nbsp;Gaurav Gupta","doi":"10.1615/JEnvironPatholToxicolOncol.2022042281","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2022042281","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer-related mortality across the globe. The most prevalent pathological form of lung cancer is non-small-cell lung cancer (NSCLC). Elevated stimulation of the PI3K/Akt/mTOR pathway causes a slew of cancer-related symptoms, making it a promising target for new anticancer drugs. The PI3K/Akt/mTOR path is involved extensively in carcinogenesis and disease advancement in NSCLC. Several new inhibitors targeting this pathway have been discovered in preclinical investigations and clinical trials. The etiology and epidemiology of NSCLC and biology of the PI3K/Akt/mTOR cascade and its role in NSCLC pathogenesis have all been discussed in this article. In this article, we've reviewed PI3K/Akt/mTOR cascade inhibitors that have been proven in vitro and in preclinical trials to be effective in NSCLC. Drugs targeting the PI3K/Akt/mTOR path in the treatment of NSCLC were also addressed. A better knowledge of the underlying molecular biology, including epigenetic changes, is also critical to detecting relevant biomarkers and guiding combination methods. Additionally, improved clinical trial designs will increase the capacity to test novel drugs and combinations for accounting for genomic variation and eventually improve patient outcomes.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"41 4","pages":"85-102"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40466515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mangiferin Inhibits Inflammation and Cell Proliferation, and Activates Proapoptotic Events via NF-κB Inhibition in DMBA-Induced Mammary Carcinogenesis in Rats.","authors":"Xin Wang, Tong Yuwen, Tian Yanqin","doi":"10.1615/JEnvironPatholToxicolOncol.2021036057","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2021036057","url":null,"abstract":"<p><p>The purpose of this study was to investigate the anti-inflammatory, antiproliferatiive, and proapoptotic molecular mechanisms of mangiferin (MGN) against mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA). Mammary cancer in rats was induced by single-dose subcutaneous injection of 0.5 ml DMBA (80 mg/kg in sesame oil) in the mammary gland. Increased tumor incidence and volume and other tumorigenic properties were observed. Further, we observed in these rats reduced antioxidant enzyme activity and elevated thiobarbituric acid reactive substance (TBARS) levels in plasma and tissues. DMBA-induced rats shows enhanced expression of the inflammatory markers NF-κBp65, COX-2, and iNOS and proliferation of PCNA and Cyclin D1, and overexpression of the antiapoptotic marker Bcl-2. Mangiferin (100 mg/kg body weight), administered orally once per day, significantly enhanced (p < 0.05) antioxidant levels and reduced TBARS levels. Moreover, MGN inhibited NF-κBp65 nucleus transcriptional activation, thereby suppressing inflammation and cell proliferation, and it increased proapoptotic proteins. Apoptosis was confirmed by TUNEL assay. In summary, MGN suppressed DMBA-induced mammary carcinogenesis through enhanced antioxidant levels, NF-κB inhibition, and positive regulation of apoptotic signals.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 2","pages":"1-9"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25564151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SHP1 Decreases Level of P-STAT3 (Ser727) and Inhibits Proliferation and Migration of Pancreatic Cancer Cells.","authors":"Mingming Zhang, Xiaoru Hu, Ye Kang, Zhe Wang, Wenyang Zhou, Chang Liu, Xianghong Yang","doi":"10.1615/JEnvironPatholToxicolOncol.2020035980","DOIUrl":"10.1615/JEnvironPatholToxicolOncol.2020035980","url":null,"abstract":"<p><strong>Purpose: </strong>To identify the direct effects and functional mechanisms of SHP1, plus its relationship with STAT3 in pancreatic cancer.</p><p><strong>Methods: </strong>Immunohistochemistry and Western blot assays were used to test SHP1 expression in pancreatic cancer. The functions of SHP1 in pancreatic cancer cells were analyzed by cell viability, colony formation, flow cytometric analysis of apoptosis, migration and invasion assays. Co-immunoprecipitation, combined with shotgun mass spectrometry, verified the direct or indirect interactions with JAK1 and p-STAT3(Ser727). Non-labeling and quantitative proteomics analysis evaluated the effect of SHP1 on protein expression levels. PRM phosphorylation modification of quantitative proteomics analysis confirmed p-STAT3(Ser727) levels.</p><p><strong>Results: </strong>SHP1 was missing or weakly expressed in human pancreatic ductal adenocarcinoma tissues and cells: PANC-1, AsPC-1, BxPC-3, and SW1990. SHP1 inhibited cell proliferation and migration. SHP1 had a slight effect on the protein expression level of PANC-1 cells. The level of p-STAT3(Ser727) was decreased by SHP1 at 0.53 multiple. Co-IP analysis revealed no direct or indirect interactions between SHP1and p-STAT3(Ser727) in protein complex patterns.</p><p><strong>Conclusion: </strong>These results suggest that SHP1 negatively regulate pancreatic cancer cells progression. It inhibits STAT3 activation by decreasing STAT3 phosphorylation at serine 727.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 1","pages":"17-27"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25409778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Troxerutin Abrogates Ischemic/Reperfusion-Induced Brain Injury through Ameliorating Oxidative Stress and Neuronal Inflammation by Inhibiting the Expression of NLRP3 in Sprague Dawley Rats.","authors":"Chao Gao,&nbsp;Yunfei Song,&nbsp;Taotao Dou,&nbsp;Shuai Jiang,&nbsp;Haoze Wu,&nbsp;Vidya Devanathadesikan Seshadri,&nbsp;Vishnu Priya Veeraraghavan,&nbsp;Pengfei Hou","doi":"10.1615/JEnvironPatholToxicolOncol.2021038860","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021038860","url":null,"abstract":"<p><p>Cerebral ischemic reperfusion (I/R) infarction is mostly associated with serious brain injury, cognitive damage, and neurological deficits. The oxidative stress mechanisms in the neurological region lead to higher reactive oxygen species production followed by oxidative stress, inflammation of neurons, and death of brain cells. The current work aims to evaluate the effect of troxerutin (TXN) on cerebral injury stimulated by I/R-induced ischemic stroke and examines the mechanistic effect of TXN on neuroinflammation in the Sprague Dawley model. The experimental rats were randomized in to four groups: (i) sham control, (ii) I/R + vehicle, (iii) I/R + 10 mg/kg bw TXN, and (iv) I/R + 20 mg/kg bw TXN. In the TXN administration and control, groups were injected intraperitoneally 15 min before reperfusion and every day for 7 days, except the sham group. Orally administered TXN (10 and 20 mg/kg/bw) modulated the water content, lowered the infarct volume, and abrogated score defects of neuron and changes in the brain tissue sample. In our study, the TXN-stimulated cerebral injury exhibited leakage of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) of the neuronal sample of tissues and showed higher antioxidant enzymes superoxide dismutase, catalase, the oxidized form of glutathione peroxidase, and the reduced form of glutathione levels. This biochemical result was additionally proved by histopathological assessment. Changes were made in antioxidant and inflammatory markers expressions interleukin-6 (IL-6), IL-4, IL-10, vascular endothelial growth factor, and cerebral induced rats. The overall findings showed that TXN protected the brain tissues from neuroinflammatory oxidative stress by reducing cerebral injury in Sprague Dawley rats. Further, the messenger RNA expression of cerebral I/R-induced animal tissues down-regulated NLRP3, caspase-1, tumor necrosis factor-α, ASC, IL-1β, and Toll-like receptor 3 (TLR3). Therefore, the TXN action on TLR3 induced brain stroke is an excellent therapeutic approach for brain damage.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 4","pages":"11-19"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39747289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of Curcumin and Quercetin in Modulation of Premature Mitochondrial Senescence and Related Changes during Lung Carcinogenesis.","authors":"Wenfu Wang,&nbsp;Ying Xie,&nbsp;Anshoo Malhotra","doi":"10.1615/JEnvironPatholToxicolOncol.2021039371","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021039371","url":null,"abstract":"<p><p>Ferroptosis is a classification of programmed cell death, which activates oxidative cell death in an iron and lipid peroxides-dependent manner. Targeting ferroptosis is a novel therapeutic approach for cancer therapy. Lung cancer is the leading cause of cancer related deaths all over the world. Circular RNAs (circRNAs), as a form of noncoding RNAs with a specific closed circular sequence are emerging as a new field in cancer research. However, the regulatory mechanisms of circRNAs in ferroptosis during lung cancer development are still elusive. In this work, we elucidate the potential prognostic value and the crucial role of circular RNA circFOXP1 in ferroptosis of lung cancer. We found that the expression of circFOXP1 was remarkably up-regulated in clinical lung sample tissues compared with adjacent tissues. The up-regulation of circFOXP1 was closely correlated with the poor overall survival of lung cancer patients. The knockdown of circFOXP1 suppressed the cell viability of lung cancer cells. The colony formation counts of lung cancer cells were repressed by the depletion of circFOXP1 as well. The Edu-positive lung cancer cells were attenuated by the silencing of circFOXP1. The migration and invasion of lung cancer cells were suppressed by circFOXP1 short hairpin RNA (shRNA). The expression of E-cadherin was enhanced, and vimentin expression was reduced by the knockdown of circFOXP1. Moreover, the treatment of ferroptosis activator erastin or RSL3 repressed the cell viability of lung cancer cells and the overexpression of circFOXP1 rescued the phenotype. The levels of malondialdehyde (MDA), iron, and lipid reactive oxygen species (ROS) were enhanced by the silencing of circFOXP1 in both erastin and RSL3-stimulated lung cancer cells. Mechanically, circFOXP1 increased SLC7A11 expression by directly sponging miR-520a-5p in lung cancer cells. The inhibitor of miR-520a-5p or the overexpression of SLC7A11 reversed circFOXP1 shRNA-induced ferroptosis phenotypes in lung cancer cells. Importantly, circFOXP1 contributed to tumor growth of lung cancer cells by enhancing SLC7A11 in vivo. Collectively, we concluded that circular RNA circFOXP1 is a potential diagnostic biomarker and contributes to malignant progression by repressing ferroptosis of lung cancer. Targeting circFOXP1 may be served as a promising therapeutic approach for lung cancer.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 4","pages":"53-60"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39747694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dialogue between Neuroinflammation and Neurodegenerative Diseases in COVID-19.","authors":"Bisruta Chowdhury,&nbsp;Apoorva Sharma,&nbsp;Sairaj Satarker,&nbsp;Jayesh Mudgal,&nbsp;Madhavan Nampoothiri","doi":"10.1615/JEnvironPatholToxicolOncol.2021038365","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021038365","url":null,"abstract":"<p><p>It has now been almost a year since the emergence of the deadly SARS-CoV-2 with millions of people losing their lives due to resultant COVID-19. Apart from the well-known consequences of respiratory illnesses, it has even effortlessly mapped itself into the nervous system through routes like blood, CSF, neurons, and olfactory cells. Interestingly, the interaction of SARS-CoV-2 with the nervous system cells like neurons, microglia, and astrocytes has been a factor to worsen COVID-19 through its neuroinflammatory actions. The release of cytokines due to astrocyte and microglial activation could progress towards the most anticipated cytokine storm proving to be detrimental in the management of COVID-19. Such hyper-inflammatory conditions could make the BBB vulnerable, encouraging excessive viral particles into the CNS, leading to further neurodegenerative pathologies like Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, and Multiple Sclerosis. Excessive neuroinflammation and neurodegeneration being the anticipated root causes of these multiple conditions, it is also essential to look into other factors that synergistically enhance the worsening of these diseases in COVID-19 patients for which additional studies are essential.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 3","pages":"37-49"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39468920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity Assessment of Transfluthrin, Benzyl Butyl Phthalate, and 17β-Estradiol on the Primary Fibroblast of the Striped Field Mouse, Apodemus agrarius.","authors":"Ji Min Lee,&nbsp;Ukjin Kim,&nbsp;Byoung-Hee Lee,&nbsp;Seo-Na Chang,&nbsp;Juha Song,&nbsp;Bokyeong Ryu,&nbsp;Jae-Hak Park","doi":"10.1615/JEnvironPatholToxicolOncol.2021036845","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021036845","url":null,"abstract":"<p><p>Environmental pollution (EP) is a well-known threat to wild animals, but its toxicological impact is poorly understood. In vitro toxicity evaluation using cells of lower predators could be a promising way to assess and monitor the effects of EPs on whole wildlife populations that are related in the food web. Here, we describe EPs' toxic effect and mechanism in the primary fibroblast derived from the embryo of the striped field mouse, Apodemus agrarius. Characterization of the primary fibroblast was via morphology, genetics, immunocytochemistry, and stable culture conditions for optimal toxicity screening. Cell viability assays-MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH)-were performed to observe cytotoxicity, and quantitative PCR was conducted to confirm gene alteration by EP exposure. MTT and LDH assays confirmed the cytotoxicity of transfluthrin (TF), benzyl butyl phthalate (BBP), and 17β-estradiol (E2) with IC50 values of 10.56 μM, 10.82 μM, and 24.08 μM, respectively, following 48-h exposures. mRNA expression of androgen-binding protein, growth hormone receptor, cytochrome C oxidase, and cytochrome P450-1A1 was induced after exposure to TF, BBP, and E2. We unveiled new EP mechanisms at the mammalian cellular level and discovered potential biomarker genes for monitoring of EPs. Based on our findings, we propose the primary fibroblast of A. agrarius as a valuable model to assess the toxicological effects of EP on wildlife.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 2","pages":"65-79"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25564157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}