| Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression. | |
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MedLine Citation:
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PMID: 20654705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Arsenic is a well-established human carcinogen; however molecular mechanisms to arsenic-induced carcinogenesis are complex and elusive. The present study identifies a potential biomarker of arsenic exposure, and redefines arsenic-induced signaling in stimulation of cell proliferation. The effect of arsenic exposure on gene expression was evaluated in PBMC of arsenic-exposed individuals selected from a severely affected district of West Bengal, India. A novel, un-documented biomarker of arsenic exposure, CyclinA was identified by microarray analysis from the study. Non-transformed cell lines HaCat and Int407 when exposed to clinically achievable arsenic concentration showed significant increase of CyclinA substantiating the clinical data. An associated increase in S phase population of cells in cell cycle, indicative of enhanced proliferation was also noticed. On further investigation of the pathway to arsenic-induced proliferation, we observed that arsenic resulted: ROS generation; activated Erk signaling; stimulated AP-1 activity, including immediate early genes, c-Jun and c-Fos. N-Acetyl-l-cysteine, a ROS quencher, blocked the arsenic-induced effects. Our study underlines a previously undefined mechanism by which arsenic imparts its toxicity and results in uncontrolled cell proliferation. |
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Authors:
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Rajdeep Chowdhury; Raghunath Chatterjee; Ashok K Giri; Chitra Mandal; Keya Chaudhuri |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-21 |
Journal Detail:
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Title: Toxicology letters Volume: 198 ISSN: 1879-3169 ISO Abbreviation: Toxicol. Lett. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-08-24 Completed Date: 2010-09-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 263-71 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Molecular & Human Genetics Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Arsenic / analysis, pharmacokinetics, toxicity* Arsenites / toxicity Blotting, Western Carcinogens, Environmental / analysis, pharmacokinetics, toxicity* Cell Culture Techniques Cell Cycle / drug effects Cell Line Cell Proliferation / drug effects* Cell Survival / drug effects Cloning, Molecular Cyclin A / biosynthesis, genetics* Environmental Exposure / analysis Epithelial Cells / drug effects, metabolism, pathology Extracellular Signal-Regulated MAP Kinases / metabolism* Hair / chemistry Humans India Keratinocytes / drug effects, metabolism, pathology Leukocytes, Mononuclear / drug effects, metabolism, pathology Luciferases / genetics Nails / chemistry Oxidative Stress / drug effects Reactive Oxygen Species / metabolism* Reverse Transcriptase Polymerase Chain Reaction Skin Diseases / chemically induced, epidemiology Sodium Compounds / toxicity Transfection Water Pollutants, Chemical / analysis, pharmacokinetics, toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Arsenites; 0/Carcinogens, Environmental; 0/Cyclin A; 0/Reactive Oxygen Species; 0/Sodium Compounds; 0/Water Pollutants, Chemical; 13768-07-5/sodium arsenite; 7440-38-2/Arsenic; EC 1.13.12.-/Luciferases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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