Document Detail


Toxicogenomic profiling of chemically exposed humans in risk assessment.
MedLine Citation:
PMID:  20382258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gene-environment interactions contribute to complex disease development. The environmental contribution, in particular low-level and prevalent environmental exposures, may constitute much of the risk and contribute substantially to disease. Systematic risk evaluation of the majority of human chemical exposures, has not been conducted and is a goal of regulatory agencies in the U.S. and worldwide. With the recent recognition that toxicological approaches more predictive of effects in humans are required for risk assessment, in vitro human cell line data as well as animal data are being used to identify toxicity mechanisms that can be translated into biomarkers relevant to human exposure studies. In this review, we discuss how data from toxicogenomic studies of exposed human populations can inform risk assessment, by generating biomarkers of exposure, early effect, and/or susceptibility, elucidating mechanisms of action underlying exposure-related disease, and detecting response at low doses. Good experimental design incorporating precise, individual exposure measurements, phenotypic anchors (pre-disease or traditional toxicological markers), and a range of relevant exposure levels, is necessary. Further, toxicogenomic studies need to be designed with sufficient power to detect true effects of the exposure. As more studies are performed and incorporated into databases such as the Comparative Toxicogenomics Database (CTD) and Chemical Effects in Biological Systems (CEBS), data can be mined for classification of newly tested chemicals (hazard identification), and, for investigating the dose-response, and inter-relationship among genes, environment and disease in a systems biology approach (risk characterization).
Authors:
Cliona M McHale; Luoping Zhang; Alan E Hubbard; Martyn T Smith
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2010-04-09
Journal Detail:
Title:  Mutation research     Volume:  705     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-02-03     Revised Date:  2011-12-21    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  172-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
School of Public Health, Divisions of Environmental Health Sciences, and Biostatistics, University of California, Berkeley, CA 94720, USA. cmchale@berkeley.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenic / toxicity
Benzene / toxicity
Environmental Exposure
Epigenesis, Genetic
Female
Gene Expression Profiling
Genomics / trends*
Humans
Male
Proteomics / methods
Risk Assessment / methods*,  trends*
Systems Biology
Toxicogenetics / trends*
Toxicology / trends*
Grant Support
ID/Acronym/Agency:
P42 ES004705-110012/ES/NIEHS NIH HHS; P42ES04705/ES/NIEHS NIH HHS; R01 ES006721-06/ES/NIEHS NIH HHS; R01ES06721/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
71-43-2/Benzene; 7440-38-2/Arsenic

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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