Toxicology in Vitro最新文献

{"title":"CircPDSS1 (hsa_circ_0017998) silencing induces ferroptosis in non-small-cell lung cancer cells by modulating the miR-137/SLC7A11/GPX4/GCLC axis","authors":"Ling Wu ,&nbsp;Ni Li ,&nbsp;Linwen Zhu ,&nbsp;Guofeng Shao","doi":"10.1016/j.tiv.2024.105887","DOIUrl":"10.1016/j.tiv.2024.105887","url":null,"abstract":"<div><h3>Background</h3><p>Circular RNAs (circRNAs) regulate the tumorigenesis of non-small-cell lung cancer (NSCLC). CircPDSS1 (hsa_circ_0017998) has been newly discovered, and its role in NSCLC remains elusive. We aimed to investigate the functional roles and downstream targets of circPDSS1 in NSCLC cells.</p></div><div><h3>Materials and methods</h3><p>Cellular viabilities were measured through the Cell Counting Kit-8 (CCK-8) assay, whereas cell death was assessed through flow cytometry. The lactate dehydrogenase activity, malondialdehyde levels, ferrous iron, and reactive oxygen species were measured using commercial assay kits. The interaction between circPDSSA/ microRNA-137 (miR-137) and miR-137/solute carrier family 7 member 11 (SLC7A11) was assayed through a dual luciferase activity assay. Finally, the mRNA and protein levels were measured using real-time reverse transcriptase-polymerase chain reaction and western blots, respectively.</p></div><div><h3>Results</h3><p>CircPDSS1 expression was upregulated in NSCLC cells, compared with healthy lung cells. CircPDSS1 silencing suppressed the viability of NSCLC cells. Additionally, circPDSS1 knockdown induced ferroptosis rather than other types of cell death in NSCLC cells. Mechanically, circPDSS1 functions as a “sponge” to inversely control miR-137 expression, which directly targets SLC7A11. Moreover, circPDSS1 silencing causes the downregulation of glutathione peroxidase 4 (GPX4) and glutamate-cysteine ligase catalytic subunit (GCLC).</p></div><div><h3>Conclusions</h3><p>Targeting the circPDSS1/miR-137/SLC7A11/GPX4/GCLC axis may be a promising strategy to kill NSCLC cells.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105887"},"PeriodicalIF":2.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human in vitro percutaneous absorption of bisphenol S: Assessment of the skin reservoir and occlusion effects","authors":"Fabrice Marquet,&nbsp;Catherine Champmartin,&nbsp;Claire Seiwert,&nbsp;Matthieu Aubertin,&nbsp;Stéphane Viton,&nbsp;Lisa Chedik,&nbsp;Frédéric Cosnier","doi":"10.1016/j.tiv.2024.105886","DOIUrl":"10.1016/j.tiv.2024.105886","url":null,"abstract":"<div><p>Bisphenol S (BPS) was introduced in many industrial and commercial applications as a presumed safer alternative to bisphenol A. However, concerns have been raised surrounding skin absorption and potential persistence of BPS and its related toxic effects in humans. A previous study revealed the likelihood of a reservoir building up in exposed skin. Here, we studied the interactions of BPS solubilized in acetone, ultrapure water, or artificial sebum with freshly excised human skin samples. <em>In vitro</em> tests were performed in static Franz diffusion cells, to explore reservoir and occlusion effects, absorption and metabolism. Most BPS passed through the skin without metabolization – &lt;10% was recovered as glucuronide or sulfate conjugates. Importantly, a substantial amount of BPS persisted in the skin, especially in the <em>stratum corneum</em>. This reservoir could lead to prolonged diffusion into the body after surface cleaning. Occlusion, that may occur with protective clothing, amplified BPS absorption up to six-fold. These findings have implications for occupational settings, highlighting the persistence of BPS contamination even after washing the skin's surface and the need to ensure protective equipment is correctly maintained and used.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105886"},"PeriodicalIF":2.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three dimensional reconstruction of skin with melanoma: A model for study of invasion in vitro","authors":"Elenn Suzany Pereira Aranha ,&nbsp;Leilane de Sousa Mendonça ,&nbsp;Bianca de Lima Almeida ,&nbsp;Emerson Lucena da Silva ,&nbsp;Felipe Pantoja Mesquita ,&nbsp;Emersom Silva Lima ,&nbsp;Ana Paula Negreiros Nunes Alves ,&nbsp;Maria Elisabete Amaral de Moraes ,&nbsp;Raquel Carvalho Montenegro ,&nbsp;Marne Carvalho de Vasconcellos","doi":"10.1016/j.tiv.2024.105883","DOIUrl":"10.1016/j.tiv.2024.105883","url":null,"abstract":"<div><p>Melanoma is a type of tumor skin with high metastatic potential. Reconstructed human skin, development for pre-clinic assay, are make using primary human cells, but with same limitations. The aim this study was to characterize a cell culture model, with structure similar to human skin containing melanoma cells entirely from cell lines. Reconstructed skin with melanoma were development using human fibroblasts (MRC5), human epidermal keratinocytes (HaCat), and human melanoma (SK-MEL-28) embedded in collagen type I. The structure was characterized by hematoxylin–eosin stained, as well as points of melanoma cell invasion, which was associated with activity of MMPs (MMP-2 and MMP-9) by zymographic method. Then, the gene expression of the target molecular mechanisms involved in melanoma progression were evaluated. Here, the model development showed a region epidermis organized and separated from the dermis, with fibroblast cells confined and melanoma cells form delimited area invasion. MMP-2 and MMP-9 were identified during of cell culture and gene expression of BRAF, NRAS, and Vimentin was confirmed. The proposed model provides one more opportunity to study in vitro tumor biology of melanoma and also to allows the study of new drugs with more reliable results then whats we would find in vivo.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105883"},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of alkylthio and arylthio derivatives of tert-butylquinone on the induction of DNA damage in a human hepatocellular carcinoma cell line (HepG2)","authors":"Jelena Djordjevic Aleksic ,&nbsp;Stoimir Kolarević ,&nbsp;Jovana Jovanović Marić ,&nbsp;Margareta Kračun-Kolarević ,&nbsp;Bojana Žegura ,&nbsp;Alja Štern ,&nbsp;Dušan Sladić ,&nbsp;Irena Novaković ,&nbsp;Branka Vuković-Gačić","doi":"10.1016/j.tiv.2024.105882","DOIUrl":"10.1016/j.tiv.2024.105882","url":null,"abstract":"<div><p>The aim of this study was to investigate the effects of <em>tert</em>-butylquinone (TBQ) and its alkylthio and arylthio derivatives on DNA in vitro, using acellular and cellular test systems. Direct interaction with DNA was studied using the plasmid pUC19. Cytotoxic (MTS assay) and genotoxic (comet assay and γH2AX focus assays) effects, and their influence on the cell cycle were studied in the HepG2 cell line. Our results show that TBQ and its derivatives did not directly interact with DNA. The strongest cytotoxic effect on the HepG2 cells was observed for the derivative 2-<em>tert</em>-butyl-5,6-(ethylenedithio)-1,4-benzoquinone (IC₅₀ 64.68 and 55.64 μM at 24-h and 48-h treatment, respectively). The tested derivatives did not significantly influence the cell cycle distribution in the exposed cellular populations. However, all derivatives showed a genotoxic activity stronger than that of TBQ in the comet assay, with 2-<em>tert</em>-butyl-5,6-(ethylenedithio)-1,4-benzoquinone producing the strongest effect. The same derivative also induced DNA double-strand breaks in the γH2AX focus assay.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105882"},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1H NMR spectroscopic characterisation of HepG2 cells as a model metabolic system for toxicology studies","authors":"Maren Jinks ,&nbsp;Emily C. Davies ,&nbsp;Berin A. Boughton ,&nbsp;Samantha Lodge ,&nbsp;Garth L. Maker","doi":"10.1016/j.tiv.2024.105881","DOIUrl":"https://doi.org/10.1016/j.tiv.2024.105881","url":null,"abstract":"<div><p>The immortalised human hepatocellular HepG2 cell line is commonly used for toxicology studies as an alternative to animal testing due to its characteristic liver-distinctive functions. However, little is known about the baseline metabolic changes within these cells upon toxin exposure. We have applied ¹H Nuclear Magnetic Resonance (NMR) spectroscopy to characterise the biochemical composition of HepG2 cells at baseline and post-exposure to hydrogen peroxide (H₂O₂). Metabolic profiles of live cells, cell extracts, and their spent media supernatants were obtained using ¹H high-resolution magic angle spinning (HR-MAS) NMR and ¹H NMR spectroscopic techniques. Orthogonal partial least squares discriminant analysis (O-PLS-DA) was used to characterise the metabolites that differed between the baseline and H₂O₂ treated groups. The results showed that H₂O₂ caused alterations to 10 metabolites, including acetate, glutamate, lipids, phosphocholine, and creatine in the live cells; 25 metabolites, including acetate, alanine, adenosine diphosphate (ADP), aspartate, citrate, creatine, glucose, glutamine, glutathione, and lactate in the cell extracts, and 22 metabolites, including acetate, alanine, formate, glucose, pyruvate, phenylalanine, threonine, tryptophan, tyrosine, and valine in the cell supernatants. At least 10 biochemical pathways associated with these metabolites were disrupted upon toxin exposure, including those involved in energy, lipid, and amino acid metabolism. Our findings illustrate the ability of NMR-based metabolic profiling of immortalised human cells to detect metabolic effects on central metabolism due to toxin exposure. The established data sets will enable more subtle biochemical changes in the HepG2 model cell system to be identified in future toxicity testing.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105881"},"PeriodicalIF":2.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001115/pdfft?md5=03f949843040e2ffb7a9ad43eac60478&pid=1-s2.0-S0887233324001115-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the combined impact of cisplatin and copper-cysteamine nanoparticles through Chemoradiation: An in-vitro study","authors":"Mahsa Ejtema ,&nbsp;Nahid Chegeni ,&nbsp;Amanollah Zarei-Ahmady ,&nbsp;Zeinab Salehnia ,&nbsp;Masoumeh Shamsi ,&nbsp;Sasan Razmjoo","doi":"10.1016/j.tiv.2024.105878","DOIUrl":"10.1016/j.tiv.2024.105878","url":null,"abstract":"<div><p>Copper-Cysteamine nanoparticles (Cu-Cy NPs) have emerged as promising radiosensitizers in cancer treatment. This study aims to investigate the combined therapeutic effect of these nanoparticles and cisplatin using a clinical linear accelerator to enhance the efficacy of chemoradiation therapy for cervical cancer.</p><p>Following successful synthesis and characterization of Cu-Cy NPs, the cytotoxicity effect of these nanoparticles and cisplatin in various concentrations was evaluated on HeLa cancer cells, individually and in combination. Additionally, the radiobiological effects of these agents were investigated under a 6MV linear accelerator.</p><p>At a concentration of 25 mg/L, Cu-Cy NPs displayed no significant cytotoxicity toward HeLa cancer cells. However, when combined with 2Gy X-ray irradiation at this concentration, the nanoparticles demonstrated a potent radiosensitizing effect. Notably, cell viability and migration rate in the combination group (Cu-Cy NPs + cisplatin + radiation) were significantly reduced compared to the radiation-alone group. Additionally, the combination treatment induced a significantly higher rate of apoptosis compared to the radiation-alone group.</p><p>Overall, Cu-Cy NPs exhibited a significant dose-dependent synergistic enhancement of radiation efficacy when combined with cisplatin under X-ray exposure, and may provide a promising approach to improve the therapeutic effect of conventional radiation therapy.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105878"},"PeriodicalIF":2.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol protects mouse hippocampal neurons from neurotoxicity induced by amyloid β-peptide25–35","authors":"Karen del Carmen Barboza Salgado ,&nbsp;Rosiene Gomes de Freitas Nascimento ,&nbsp;Pedro José Fernandes Nunes Coelho ,&nbsp;Laser Antonio Machado Oliveira ,&nbsp;Katiane Oliveira Pinto Coelho Nogueira","doi":"10.1016/j.tiv.2024.105880","DOIUrl":"10.1016/j.tiv.2024.105880","url":null,"abstract":"<div><p>Alzheimer's disease (AD), the most prevalent form of dementia worldwide, is a significant health concern, according to the World Health Organization (WHO). The neuropathological diagnostic criteria for AD are based on the deposition of amyloid-β peptide (Aβ) and the formation of intracellular tau protein tangles. These proteins are associated with several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, lipid peroxidation, reduced neuronal viability, and cell death. In this context, our study focuses on the potential therapeutic use of cannabidiol (CBD), a non-psychotropic cannabinoid with antioxidant and anti-inflammatory effects. We aim to evaluate CBD's neuroprotective role, particularly in protecting hippocampal neurons from Aβ₂₅_–₃₅-induced toxicity. Our findings indicate that CBD significantly improves cell viability and decreases levels of lipid peroxidation and oxidative stress. The results demonstrate that CBD possesses a robust potential to rescue cells from induced neurotoxicity through its antioxidant properties. Additionally, the neuroprotective effect of CBD may be associated with the modulation of the endocannabinoid system. These findings suggest that CBD could be a promising compound for adjuvant treatments in neurodegenerative processes triggered by amyloid-β peptide.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105880"},"PeriodicalIF":2.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of an in vitro simulated one compartment extravascular administration model and its comparison with classic in vitro administration model in copper chloride induced HepG2 cell death","authors":"Lailai Yan ,&nbsp;Dawei Fu ,&nbsp;Jie Chen ,&nbsp;Mingmei Hao ,&nbsp;Juanling Fu ,&nbsp;Biyun Yao ,&nbsp;Weidong Hao ,&nbsp;Peng Zhao","doi":"10.1016/j.tiv.2024.105879","DOIUrl":"https://doi.org/10.1016/j.tiv.2024.105879","url":null,"abstract":"<div><p>In this study, we designed an in vitro administration device based on compartment model theory and utilized it to construct an in vitro simulated one compartment extravascular administration model of copper chloride. Within the <em>C</em>_<em>max</em> range of 3.91–1000.00 μM, the measured concentration-time curves of the simulated one compartment extravascular administration model almost coincide with the corresponding theoretical curves. The measured values of toxicokinetic parameters, including <em>k</em>_<em>e</em>, <em>T</em>_<em>1/2</em>, <em>k</em>_a, <em>T</em>_{<em>1/2a</em>}, <em>T</em>_<em>max</em>, <em>C</em>_<em>max</em>, <em>CL</em>, and <em>AUC</em>_{<em>0-∞</em>} are close to the corresponding theoretical values. The fitting coefficients are &gt;0.9990. In simulated one compartment extravascular administration and classic in vitro administration, copper chloride dose-dependently induced HepG2 cell death. When <em>C</em>_<em>max</em>/administration concentration is equal, classic in vitro administration induces a higher cell death rate than simulated one compartment extravascular administration. However, there is no significant difference in inducing cell death between the two administration models when area under the curve is equal. In conclusion, the device designed in this study can be used to in vitro simulate one compartment extravascular administration, making in vitro toxicity testing more similar to in vivo scenarios. There are differences in copper chloride induced HepG2 cell death between simulated one compartment extravascular administration and classic in vitro administration.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105879"},"PeriodicalIF":3.2,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity","authors":"Shi-Cai Gao ,&nbsp;Ming-Zhe Dong ,&nbsp;Bing-Wang Zhao ,&nbsp;Sai-Li Liu ,&nbsp;Jia-Ni Guo ,&nbsp;Si-Min Sun ,&nbsp;Yuan-Yuan Li ,&nbsp;Yuan-Hong Xu ,&nbsp;Zhen-Bo Wang","doi":"10.1016/j.tiv.2024.105876","DOIUrl":"10.1016/j.tiv.2024.105876","url":null,"abstract":"<div><p>Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species. Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105876"},"PeriodicalIF":2.6,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of long-term inorganic arsenic exposure on erythropoietin production in vitro","authors":"Md. Anamul Haque,&nbsp;Akari Yoshimoto,&nbsp;Hiroshi Nakagawa,&nbsp;Kazuhiko Nishimura","doi":"10.1016/j.tiv.2024.105877","DOIUrl":"10.1016/j.tiv.2024.105877","url":null,"abstract":"<div><p>Arsenic is widely present in the environment in trivalent and pentavalent forms; long-term arsenic exposure due to environmental pollution has become a problem. Previous reports have shown that 24-h exposure to arsenate (as pentavalent arsenic) potentiates erythropoietin (EPO) production via reactive oxygen species (ROS) in EPO-producing HepG2 cells. However, the effects of <em>long-term</em> arsenate exposure on EPO production remain unclear. In HepG2 cells subcultured for 3 weeks in the presence of arsenate, <em>EPO</em> mRNA levels were lower than those in untreated cells. Levels of <em>ARSENITE METHYLTRANSFERASE</em> mRNA, as well as those of Nuclear factor erythroid 2-related factor 2, glutathione, and superoxide dismutase proteins, were increased compared to untreated cells, but levels of malondialdehyde were not significantly altered. Thus, long-term exposure to arsenate enhances ROS scavenging, suggesting that the ROS-induced accumulation of <em>EPO</em> mRNA is attenuated by arsenate exposure. The induction of EPO accumulation by hypoxia also was attenuated by long-term arsenate exposure, suggesting an impairment in responsivity of EPO production. Furthermore, mRNA levels of <em>SIRTUIN-1</em>, which affects <em>EPO</em> transcription, were potentiated by long-term arsenate exposure. These results suggest that long-term arsenate exposure has multiple, distinct effects on EPO production in vitro.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105877"},"PeriodicalIF":3.2,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}