Document Detail


Use of the γH2AX assay for assessing the genotoxicity of polycyclic aromatic hydrocarbons in human cell lines.
MedLine Citation:
PMID:  20832459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The development of in vitro genotoxic assays as an alternative method to animal experimentation is of growing interest in the context of the implementation of new regulations on chemicals. However, extrapolation of toxicity data from in vitro systems to in vivo models is hampered by the fact that in vitro systems vary in their capability to metabolize chemicals, and that biotransformation can greatly influence the experimental results. Therefore, much attention has to be paid to the cellular models used and experimental conditions. Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic ubiquitous pollutants. Human exposure to PAHs is mainly from food origin. In this study, a detailed analysis of the biotransformation capabilities of three human cell lines commonly used for in vitro testing (HepG2, ACHN and Caco-2) was undertaken using 3 model PAHs (benzo(a)pyrene [B(a)P], fluoranthene [FLA] and 3-methylcholanthrene [3-MC]). Concomitantly the genotoxicity of these PAHs was investigated in different cell lines, using a new genotoxic assay (H2AX) in 96-well plates. The metabolic rates of B(a)P, FLA and 3-MC were similar in HepG2 and Caco-2 cell lines, respectively, though with the production of different metabolites. The ACHN cell line was shown to express very limited metabolic capabilities. We demonstrated that the PAHs having a high metabolic rate (B(a)P and 3-MC) were genotoxic from 10(-7) molar in both HepG2 and Caco-2 cells. The present study shows that H2AX measurement in human cell lines competent for the metabolism, is an efficient and sensitive genotoxic assay requiring less cells and time than other currently available tests.
Authors:
M Audebert; A Riu; C Jacques; A Hillenweck; E L Jamin; D Zalko; J-P Cravedi
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Publication Detail:
Type:  Journal Article     Date:  2010-09-09
Journal Detail:
Title:  Toxicology letters     Volume:  199     ISSN:  1879-3169     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  182-92     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
INRA, UMR 1089 Xénobiotiques INRA-ENVT, Toulouse, France. marc.audebert@toulouse.inra.fr
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MeSH Terms
Descriptor/Qualifier:
Benzo(a)pyrene / metabolism,  toxicity
Cell Line, Tumor
Chromatography, High Pressure Liquid
DNA Damage
Fluorenes / metabolism,  toxicity
Histones / analysis*
Humans
Immunohistochemistry
Methylcholanthrene / metabolism,  toxicity
Mutagenicity Tests*
Phosphorylation
Polycyclic Hydrocarbons, Aromatic / metabolism,  toxicity*
Chemical
Reg. No./Substance:
0/Fluorenes; 0/H2AFX protein, human; 0/Histones; 0/Polycyclic Hydrocarbons, Aromatic; 206-44-0/fluoranthene; 50-32-8/Benzo(a)pyrene; 56-49-5/Methylcholanthrene

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


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