المؤلفون: Kai Yue, Yansheng Wu, Beibei Ye, Peng Chen, Qingchuan Lai, Xudong Wang, Chao Jing, Yue Wu, Mengqian Zhou, Yuansheng Duan, Xingchen Li, Xiaofeng Yao, Dandan Liu, Hong Li, Linqi Li, Shengchi Zhang

المصدر: Theranostics

مصطلحات موضوعية: Male, 0301 basic medicine, Esophageal Neoplasms, Carcinogenesis, Medicine (miscellaneous), Snail, medicine.disease_cause, Metastasis, Mice, 0302 clinical medicine, Cell Movement, PSMD14, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, biology, SNAIL, EMT, Esophageal cancer, Pyrrolidinones, Up-Regulation, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Chemosensitivity, Research Paper, medicine.drug, Proteasome Endopeptidase Complex, Epithelial-Mesenchymal Transition, Mice, Nude, Antineoplastic Agents, 03 medical and health sciences, Downregulation and upregulation, Esophageal squamous cell carcinoma, In vivo, Cell Line, Tumor, biology.animal, Biomarkers, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Cell Proliferation, Cisplatin, business.industry, Ubiquitination, medicine.disease, Thiolutin, 030104 developmental biology, Trans-Activators, Cancer research, Snail Family Transcription Factors, business

الوصف: Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC. Methods: Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using in vitro and in vivo experiments. Immunoprecipitation and in vivo ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14. Results: Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of in vitro and in vivo assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer. Conclusion: Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c47c33d3831d41492d14a4c177dc6b7Test
https://doi.org/10.7150/thno.46109Test

المؤلفون: Xudong Wang, Mengqian Zhou, Wenchao Zhang, Hui Wei, Xiaofeng Yao, Beibei Ye, Chao Jing, Yuansheng Duan, Xingchen Li, Shanshan Zhuo, Kai Yue, Yansheng Wu, Dandan Liu, Linqi Li, Qingchuan Lai

المصدر: Theranostics

مصطلحات موضوعية: 0301 basic medicine, Carcinogenesis, Medicine (miscellaneous), medicine.disease_cause, Deubiquitinating enzyme, Mice, 0302 clinical medicine, PSMD14, E2F1, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, Deubiquitinating Enzymes, Prognosis, Pyrrolidinones, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Chemoresistance, medicine.drug, Research Paper, Proteasome Endopeptidase Complex, Mice, Nude, Biology, 03 medical and health sciences, stomatognathic system, Cell Line, Tumor, medicine, otorhinolaryngologic diseases, Animals, Humans, Protein kinase B, neoplasms, PI3K/AKT/mTOR pathway, Cell Proliferation, Squamous Cell Carcinoma of Head and Neck, SOXB1 Transcription Factors, Ubiquitination, Head and neck squamous cell carcinoma, medicine.disease, Thiolutin, Head and neck squamous-cell carcinoma, stomatognathic diseases, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, biology.protein, Trans-Activators, Chromatin immunoprecipitation, Proto-Oncogene Proteins c-akt, E2F1 Transcription Factor

الوصف: Increasing evidence reveals a close relationship between deubiquitinating enzymes (DUBs) and cancer progression. In this study, we attempted to identify the roles and mechanisms of critical DUBs in head and neck squamous cell carcinoma (HNSCC). Methods: Bioinformatics analysis was performed to screen differentially expressed novel DUBs in HNSCC. Immunohistochemistry assay was used to measure the expression of DUB PSMD14 in HNSCC specimens and adjacent normal tissues. The level of PSMD14 in HNSCC tumorigenesis was investigated using a 4-NQO-induced murine HNSCC model. The function of PSMD14 was determined through loss-of-function assays. Chromatin immunoprecipitation, immunoprecipitation and in vivo ubiquitination assay were conducted to explore the potential mechanism of PSMD14. The anti-tumor activity of PSMD14 inhibitor Thiolutin was assessed by in vitro and in vivo experiments. Results: We identified PSMD14 as one of significantly upregulated DUBs in HNSCC tissues. Aberrant expression of PSMD14 was associated with tumorigenesis and malignant progression of HNSCC and further indicated poor prognosis. The results of in vitro and in vivo experiments demonstrated PSMD14 depletion significantly undermined HNSCC growth, chemoresistance and stemness. Mechanically, PSMD14 inhibited the ubiquitination and degradation of E2F1 to improve the activation of Akt pathway and the transcription of SOX2. Furthermore, PSMD14 inhibitor Thiolutin exhibited a potent anti-tumor effect on HNSCC in vivo and in vitro by impairing DUB activity of PSMD14. Conclusion: Our findings demonstrate the role and mechanism of PSMD14 in HNSCC, and provide a novel and promising target for diagnosis and clinical therapy of HNSCC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41457b31fc40f3f3f83e381a98fab731Test
http://europepmc.org/articles/PMC7806466Test

المؤلفون: Rui Jin, Xuan Zhou, Xiaofeng Yao, Qiang Zhang, Ping Li, Chao Jing, Yu Wang, Wenchao Zhang, Yuansheng Duan, Xudong Wang, Yingjie Tao

المصدر: Cancer Letters. 432:38-46

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Adenoid cystic carcinoma, Perineural invasion, Mice, Nude, Motility, Apoptosis, medicine.disease_cause, Metastasis, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Tumor Cells, Cultured, medicine, Animals, Humans, Cell Proliferation, Mice, Inbred BALB C, Mutation, business.industry, Liver Neoplasms, NF-kappa B, Zinc Finger E-box-Binding Homeobox 1, NF-κB, Prognosis, Salivary Gland Neoplasms, medicine.disease, Carcinoma, Adenoid Cystic, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Survival Rate, Insulin-Like Growth Factor Binding Protein 2, 030104 developmental biology, Oncology, chemistry, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, business, Nuclear localization sequence, Signal Transduction

الوصف: Metastasis is a major cause of poor prognosis in patients suffered with salivary adenoid cystic carcinoma (SACC), in which many factors are implicated. In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF-κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC. In addition, IGFBP2 mutation in the nuclear localization signal could impede nuclear translocation of p65, lower ZEB1 expression, and abrogate the EMT process. In xenograft models, IGFBP2 overexpression promoted lung and liver metastases of SACC cells; while if nuclear IGFBP2 was reduced, the formation of metastases in lung and liver was weakened. Together, these results for the first time demonstrate that IGFBP2 plays an important role in invasion and metastasis of SACC through the NF-κB/ZEB1 signaling pathway and IGFBP2 may be a novel biomarker and target for SACC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d4ac1ce9543ace508a445463d56d618Test
https://doi.org/10.1016/j.canlet.2018.06.008Test

المؤلفون: Xiaoming Liu, Guang Yang, Xiaofeng Yao, Qinghua Sun, Liping Jiang, Min Chen, X Gao, Shaopeng Wang, Xiance Sun

المصدر: Human & Experimental Toxicology. 36:1177-1185

مصطلحات موضوعية: 0301 basic medicine, DNA damage, Health, Toxicology and Mutagenesis, Catechols, Gene Expression, Toxicology, medicine.disease_cause, Umbilical vein, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Diethylhexyl Phthalate, Malondialdehyde, Human Umbilical Vein Endothelial Cells, medicine, Humans, chemistry.chemical_classification, Reactive oxygen species, Molecular Structure, biology, Superoxide Dismutase, General Medicine, Glutathione, Molecular biology, Comet assay, Checkpoint Kinase 2, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Comet Assay, Fatty Alcohols, Tumor Suppressor Protein p53, Reactive Oxygen Species, Oxidative stress, DNA Damage

الوصف: Mono (2-ethylhexyl) phthalate (MEHP) is the principal metabolite of di (2-etylhexyl) phthalate, which is widely used as a plasticizer, especially in medical devices. MEHP has toxic effects on cardiovascular system. The aim of this study was to investigate the possibility that 6-gingerol may inhibit the oxidative DNA damage of MEHP in human umbilical vein endothelial cells (HUVECs) and the potential mechanism. The comet assay was used to monitor DNA strand breaks. We have shown that 6-gingerol significantly reduced the DNA strand breaks caused by MEHP. MEHP increased the levels of reactive oxygen species and malondialdehyde, decreased the level of glutathione and activity of superoxide dismutase, and altered the mitochondrial membrane potential. In addition, DNA damage-associated proteins (p53 and p-Chk2 (T68)) were significantly increased by the treatment of MEHP. Those effects can all be protected by 6-gingerol. The results firmly indicate that 6-gingerol may have a strong protective ability against the DNA damage caused by MEHP in HUVECs, and the mechanism may relate to the antioxidant activity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6047f202225368d680080ad5e1076c1eTest
https://doi.org/10.1177/0960327116681650Test

المؤلفون: Xiaoxia Shi, Jun Cao, Chengyan Geng, Zhiguo Li, Yong Liu, Xiaofeng Yao, Qiujuan Li, Liping Jiang, Wei Lv

المصدر: Free radical biologymedicine. 130

مصطلحات موضوعية: Autophagy-Related Proteins, Apoptosis, Mitochondrion, medicine.disease_cause, Biochemistry, Downregulation and upregulation, Physiology (medical), medicine, Autophagy, Humans, Inducer, A549 cell, Membrane Potential, Mitochondrial, Chemistry, Caspase 3, Caspase 9, Cell biology, Mitochondria, Gene Expression Regulation, Neoplastic, Crosstalk (biology), Cysteine Endopeptidases, Proto-Oncogene Proteins c-bcl-2, A549 Cells, Beclin-1, Carcinogenesis, Cadmium

الوصف: Cadmium (Cd) is a highly ubiquitous detrimental metal in the environment. It is a well-known inducer of tumorigenesis, but the mechanism is not clear. In our previous study, we found that ROS-dependent Atg4B upregulation mediated Cd-induced autophagy and autophagy played an important role in Cd-induced proliferation and invasion in A549 cells. In this study, we found that Cd induced both apoptosis and autophagy in A549 cells, and apoptosis preceded autophagy. Z-VAD-FMK repressed Cd-induced LC3 and Beclin1, indicating that apoptosis was essential for Cd-induced autophagy. 3MA destroyed the recovery of mitochondrial membrane potential and increased Cd-induced CL-CASP9 and CL-CASP3 expression, suggesting that Cd-induced autophagy prevented A549 cells from apoptosis. Further study showed that Atg4B upregulation was mediated by mitochondrial dysfunction and conversely affected mitochondrial function by decreasing Bcl-2 protein expression and its localization in mitochondria, and played an important role in Cd-induced apoptosis. Moreover, Bcl-2 was involved in Cd-induced autophagy. Co-IP assay showed that Atg4B could directly bind to Bcl-2, and consequently promote disassociation of Bcl-2-Beclin1 and released autophagic protein Beclin1 to activate autophagic pathway. Taken together, our results demonstrated that the interaction of Atg4B and Bcl-2 might play an important role in Cd-induced crosstalk between apoptosis and autophagy through disassociation of Bcl-2-Beclin1. Cd-induced autophagy is apoptosis-dependent and prevents apoptotic cell death to ensure the growth and proliferation of A549 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b138bcb16e006f225ed0791caf2718f8Test
https://pubmed.ncbi.nlm.nih.gov/30458278Test

المؤلفون: Jun Cao, Chengyan Geng, Yue Ding, Xiaofeng Yao, Laifu Zhong, Liping Jiang, Chunpeng Gao

المصدر: Toxicology in Vitro. 28:667-674

مصطلحات موضوعية: Cell Survival, Apoptosis, Mitochondrion, Toxicology, medicine.disease_cause, Cathepsin B, Lysosome, medicine, Humans, Cathepsin, biology, Cytochrome c, Hydrazones, Cytochromes c, Dipeptides, Hep G2 Cells, General Medicine, Mitochondria, Cell biology, medicine.anatomical_structure, Nitroimidazoles, Tacrine, biology.protein, Cholinesterase Inhibitors, Lysosomes, Reactive Oxygen Species, Oxidative stress, medicine.drug

الوصف: Tacrine (THA) is a competitive inhibitor of cholinesterase. Administration of THA for the treatment of Alzheimer’s disease results in a reversible hepatotoxicity in 30–50% of patients, as indicated by elevated alanine aminotransferase levels. However, the intracellular mechanisms have not yet been elucidated. In our previous study, we found that THA induced cytotoxicity and mitochondria dysfunction by ROS generation and 8-OHdG formation in mitochondrial DNA in HepG2 cells. In this study, the mechanism underlying was further investigated. Our results demonstrated that THA induced dose-dependent apoptosis with cytochrome c release and activation of caspase-3. THA-induced apoptosis was inhibited by treating cells with a ROS inhibitor, YCG063. In addition, we observed that THA led to an early lysosomal membrane permeabilization and release of cathepsin B. Pretreatment with CA-074Me, a specific cathepsin B inhibitor resulted in a significant but not complete decrease in tacrine-induced apoptosis. These data suggest that tacrine-induced cell apoptosis involves both mitochondrial damage and lysosomal membrane destabilization, and ROS is the critical factor that integrates tacrine-induced mitochondrial and lysosomal death pathways.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ab2e7bd26ce279f3d17549ea6b0c595Test
https://doi.org/10.1016/j.tiv.2014.02.001Test

المؤلفون: Xiaofang Liu, Xiaofeng Yao, Guang Yang, Shaopeng Wang, Xiance Sun, Liping Jiang, Qinghua Sun, Min Chen

المصدر: Chemico-biological interactions. 256

مصطلحات موضوعية: 0301 basic medicine, Catechols, Apoptosis, Biology, Ginger, Toxicology, medicine.disease_cause, Protective Agents, 03 medical and health sciences, 0302 clinical medicine, medicine, Autophagy, Human Umbilical Vein Endothelial Cells, Humans, Protein kinase B, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Reactive oxygen species, TOR Serine-Threonine Kinases, Endothelial Cells, General Medicine, Hydrogen Peroxide, Cell biology, Oxidative Stress, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Signal transduction, Fatty Alcohols, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt, Oxidative stress, Signal Transduction

الوصف: 6-Gingerol, the major pharmacologically-active component of ginger, has the potential to prevent heart disease. However, the mechanisms are not well understood. In this study, the protective effect of 6-gingerol against hydrogen peroxide-induced apoptosis in human umbilical vein endothelial cells (HUVECs) was investigated. Apoptosis was detected by Hoechst 33342 and Flow cytometry analysis. To further elucidate the crosstalk between apoptosis and autophagy, we tested the expression of autophagy related proteins, LC3B, Bcl-2, Beclin1, AKT, p-AKT, mechanistic target of rapamycin (mTOR), and p-mTOR. Furthermore, mitochondrial membrane potential and the intracellular generation of reactive oxygen species (ROS) were also investigated. Our data revealed that 6-gingerol significantly reduced apoptosis by inducing autophagy. It has been demonstrated that 6-gingerol suppressed the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, increased the expression of Beclin1 to promote autophagy, and increased Bcl-2 expression to inhibit apoptosis. In addition, the damage of mitochondrial was protected, and ROS level was decreased by 6-gingerol. These firmly indicate 6-gingerol has a strong protective ability against the apoptosis caused by oxidative stress in HUVECs, and the mechanism may relate to the induction of autophagy. Our data suggest 6-gingerol may be beneficial in the prevention of atherosclerosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f64d5814f57c1f7a8037362a7405e1eTest
https://pubmed.ncbi.nlm.nih.gov/27451028Test

المؤلفون: Wenyu Guo, Xiaofeng Yao, Xuan Zhou, Shanshan Sun, Lun Zhang

المصدر: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 37(2)

مصطلحات موضوعية: 0301 basic medicine, Oncogene, Mechanism (biology), Carcinogenesis, Cancer, General Medicine, Biology, Bioinformatics, medicine.disease_cause, medicine.disease, Biomarker (cell), Metastasis, 03 medical and health sciences, Insulin-Like Growth Factor Binding Protein 2, 030104 developmental biology, 0302 clinical medicine, Tumor progression, 030220 oncology & carcinogenesis, Neoplasms, medicine, Animals, Humans, Signal transduction, Signal Transduction

الوصف: Insulin-like growth factor (IGF)-binding protein 2(IGFBP2), a key member of IGF family, has been reported as a notable oncogene in most human epithelium cancers. Increasing evidences suggested that IGFBP2 might be a candidate target of therapuetic potential by regulating key cancer metastasis and invasion-associated signaling networks, but there is still confusion about the mechanism on how IGFBP2 takes part in these processes. In this review, we summarized the current points of view that IGFBP2 functions in signaling pathways during tumorigenesis and tumor progression and discussed its potential clinical applications as a therapeutic target.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d12bb2a2294c6fc2a90940aa8df68a89Test
https://pubmed.ncbi.nlm.nih.gov/26662106Test

المؤلفون: Chengyan Geng, Jun Cao, Xiang Xin Xue, Xiaomei Zhang, Liping Jiang, Xiaofeng Yao, Laifu Zhong

المصدر: Journal of Trace Elements in Medicine and Biology. 22:189-195

مصطلحات موضوعية: Lipopolysaccharides, Antioxidant, Lipopolysaccharide, medicine.medical_treatment, Inflammation, Pharmacology, medicine.disease_cause, Biochemistry, Monocytes, Cell Line, Inorganic Chemistry, chemistry.chemical_compound, Boric Acids, medicine, Humans, Secretion, RNA, Messenger, Sulfhydryl Compounds, Buthionine Sulfoximine, Tumor Necrosis Factor-alpha, Chemistry, Glutathione, Acetylcysteine, Gene Expression Regulation, Molecular Medicine, Tumor necrosis factor alpha, medicine.symptom, Oxidative stress, Intracellular

الوصف: Oxidative stress plays an important role during inflammatory diseases and antioxidant administration to diminish oxidative stress may arrest inflammatory processes. Boron has been implicated to modulate certain inflammatory mediators and regulate inflammatory processes. Here we investigated the role of the tripeptide glutathione (GSH) in modulating the effects of boric acid (BA) on lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) formation in THP-1 monocytes. Interestingly, we found that BA had no significant effects on both TNF-alpha production and intracellular GSH contents, whereas it could inhibit LPS-induced TNF-alpha formation and ameliorated the d,l-buthionine-S,R-sulfoximine (BSO)-induced GSH depletion. Twenty-four hour incubation with BSO induced a decrease of the intracellular GSH and an increase of TNF-alpha. Treatment with N-acetyl-l-cysteine (NAC) did not significantly increase intracellular content of GSH but significantly reduced the secretion of TNF-alpha. BSO-pretreatment for 24h enhanced the LPS-induced secretion and mRNA expression of TNF-alpha further. BA inhibited LPS-stimulated TNF-alpha formation was also seen after GSH depletion by BSO. These results indicate that BA may have anti-inflammatory effect in the LPS-stimulated inflammation and the effect of BA on TNF-alpha secretion may be induced via a thiol-dependent mechanism.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b312266ad9b1957250a299e7c1b4a9e9Test
https://doi.org/10.1016/j.jtemb.2008.03.005Test

المؤلفون: Laifu Zhong, Xiaofeng Yao

المصدر: Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 587:38-44

مصطلحات موضوعية: Carcinoma, Hepatocellular, Health, Toxicology and Mutagenesis, Biology, medicine.disease_cause, Risk Assessment, chemistry.chemical_compound, Dichlorofluorescein, Tumor Cells, Cultured, Genetics, medicine, Humans, Carcinogen, chemistry.chemical_classification, Fluorocarbons, Reactive oxygen species, Micronucleus Tests, Mutagenicity Tests, Liver Neoplasms, Molecular biology, Comet assay, Oxidative Stress, chemistry, Cell culture, Micronucleus test, Perfluorooctanoic acid, Comet Assay, Caprylates, Reactive Oxygen Species, Oxidative stress, DNA Damage

الوصف: Perfluorooctanoic acid (C 8 HF 15 O 2 , PFOA) is widely used in various industrial fields for decades and it is environmentally bioaccumulative. PFOA is known as a potent hepatocarcinogen in rodents. But it is not yet clear whether it is also carcinogenic in humans, and the genotoxic effects of PFOA on human cells have not yet been examined. In this study, the genotoxic potential of PFOA was investigated in human hepatoma HepG2 cells in culture using single cell gel electrophoresis (SCGE) assay and micronucleus (MN) assay. In order to clarify the underlying mechanism(s) we measured the intracellular generation of reactive oxygen species (ROS) using dichlorofluorescein diacetate as a fluorochrome. The level of oxidative DNA damage was evaluated by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) in PFOA-treated HepG2 cells. PFOA at 50–400 μM caused DNA strand breaks and at 100–400 μM MN in HepG2 cells both in a dose-dependent manner. Significantly increased levels of ROS and 8-OHdG were observed in these cells. We conclude that PFOA exerts genotoxic effects on HepG2 cells, probably through oxidative DNA damage induced by intracellular ROS.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54a5f447623b1af847f90f8c88fcf516Test
https://doi.org/10.1016/j.mrgentox.2005.07.010Test