|Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression.|
|PMID: 20654705 Owner: NLM Status: MEDLINE|
|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.|
|Rajdeep Chowdhury; Raghunath Chatterjee; Ashok K Giri; Chitra Mandal; Keya Chaudhuri|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-21|
|Title: Toxicology letters Volume: 198 ISSN: 1879-3169 ISO Abbreviation: Toxicol. Lett. Publication Date: 2010 Oct|
|Created Date: 2010-08-24 Completed Date: 2010-09-10 Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands|
|Languages: eng Pagination: 263-71 Citation Subset: IM|
|Copyright 2010 Elsevier Ireland Ltd. All rights reserved.|
|Molecular & Human Genetics Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India.|
|APA/MLA Format Download EndNote Download BibTex|
Arsenic / analysis, pharmacokinetics, toxicity*
Arsenites / toxicity
Carcinogens, Environmental / analysis, pharmacokinetics, toxicity*
Cell Culture Techniques
Cell Cycle / drug effects
Cell Proliferation / drug effects*
Cell Survival / drug effects
Cyclin A / biosynthesis, genetics*
Environmental Exposure / analysis
Epithelial Cells / drug effects, metabolism, pathology
Extracellular Signal-Regulated MAP Kinases / metabolism*
Hair / chemistry
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
Water Pollutants, Chemical / analysis, pharmacokinetics, toxicity*
|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 18.104.22.168/Extracellular Signal-Regulated MAP Kinases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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