Document Detail


Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression.
MedLine Citation:
PMID:  20654705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rajdeep Chowdhury; Raghunath Chatterjee; Ashok K Giri; Chitra Mandal; Keya Chaudhuri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-21
Journal Detail:
Title:  Toxicology letters     Volume:  198     ISSN:  1879-3169     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2010 Oct 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  263-71     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Molecular & Human Genetics Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / 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:
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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