Document Detail


Evaluation of a proposed in vitro test strategy using neuronal and non-neuronal cell systems for detecting neurotoxicity.
MedLine Citation:
PMID:  16959468     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The European Commission White Paper, "Strategy for a future chemicals policy" (EC, 2001) is estimated to require the testing of approximately 30,000 "existing" chemicals by 2012. Recommended in vitro tests require validation. As the White Paper (EC, 2001) requires neurotoxic data, this study evaluated an in vitro testing strategy for predicting in vivo neurotoxicity. The sensitivities of differentiated PC12 cells and primary cerebellum granule cells (CGC) were compared to undifferentiated PC12 cells which can indicate basal cytotoxicity. Cytotoxicants and neurotoxicants selected for testing covered a range of mechanisms and potencies. Neurotoxicants were not distinguished from cytotoxicants despite significantly different cell system responses using all endpoints; cell viability/activity, ATP depletion, MMP depolarisation, ROS production and cytoskeleton modifications. For all chemicals tested, neuronal-like cell systems were generally less sensitive than undifferentiated PC12 cells. Acute oral rodent LD(50) values correlated with cytotoxicity IC(50) values for the respective chemicals tested in each cell system. This study concluded that although simple non-specific assays are required to distinguish basal cytotoxicity from specific neurotoxicity by using different cell systems with different states of neuronal differentiation, further work is required to determine suitable combinations of cell systems and endpoints capable of distinguishing neurotoxicants from cytotoxicants.
Authors:
J Gartlon; A Kinsner; A Bal-Price; S Coecke; R H Clothier
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-07-29
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  20     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-10-18     Completed Date:  2006-12-26     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1569-81     Citation Subset:  IM    
Affiliation:
ECVAM, European Commission Joint Research Centre, Via E. Fermi 1, Ispra 21020, Italy. jgartlon@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Benzimidazoles
Carbocyanines
Cell Line
Cell Separation
Cerebellum / cytology
Cytoskeleton / drug effects,  ultrastructure
Enzyme-Linked Immunosorbent Assay
Fluorescent Dyes
Glial Fibrillary Acidic Protein / metabolism
Indicators and Reagents
Lethal Dose 50
Neurofilament Proteins / metabolism
Neurons / drug effects*
Neurotoxicity Syndromes / pathology*
Neurotoxins / toxicity*
Oxazines
PC12 Cells
Rats
Xanthenes
Chemical
Reg. No./Substance:
0/Benzimidazoles; 0/Carbocyanines; 0/Fluorescent Dyes; 0/Glial Fibrillary Acidic Protein; 0/Indicators and Reagents; 0/Neurofilament Proteins; 0/Neurotoxins; 0/Oxazines; 0/Xanthenes; 21527-78-6/5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; 550-82-3/resazurin; 56-65-5/Adenosine Triphosphate

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


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