Document Detail

Domoic acid induces direct DNA damage and apoptosis in Caco-2 cells: recent advances.
MedLine Citation:
PMID:  18293405     Owner:  NLM     Status:  MEDLINE    
Domoic acid (DA) is a neurotoxin produced by sea-water phytoplankton. Shellfish feeding on the phytoplankton can bioconcentrate DA, leading to a potentially serious health hazard for people consuming the contaminated shellfish. DA is the principal toxin responsible for amnesic shellfish poisoning (ASP). The toxic mechanism of DA is believed to be mediated at the level of the mitochondria, where uncoupling of oxidative phosphorylation decreases membrane permeability, causing cell swelling and ultimately lysis. Literature is poor concerning data on the possible genotoxicity and cytotoxicity of DA. In the present study, we have evaluated the cytotoxicity and genotoxicity of DA on a human colorectal adenocarcinoma cell line (Caco-2). Our results clearly demonstrate that DA decreased cell viability (IC(50) about 70 ng/mL), induced direct DNA damage from 15 ng/mL, and apoptosis in Caco-2 cells at 100 ng/mL. This apoptosis is likely bax-dependent and occurred only at high concentrations of DA, while lower concentrations upregulated both bax and bcl-2 at an apparent constant ratio until a sudden decrease of bcl-2 at 100 ng/mL and increase of bax.
C R Carvalho Pinto-Silva; S Moukha; W G Matias; E E Creppy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Environmental toxicology     Volume:  23     ISSN:  1522-7278     ISO Abbreviation:  Environ. Toxicol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-10     Completed Date:  2009-01-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100885357     Medline TA:  Environ Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  657-63     Citation Subset:  IM    
Copyright Information:
2008 Wiley Periodicals, Inc.
Toxicology Department, UFR of Pharmaceutical Sciences, University of Bordeaux 2, France.
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MeSH Terms
Apoptosis / drug effects*
Base Sequence
Caco-2 Cells
Cell Survival / drug effects
DNA Damage / drug effects*
Foodborne Diseases
Genes, bcl-2 / drug effects*,  physiology
Inhibitory Concentration 50
Kainic Acid / analogs & derivatives*,  toxicity
Marine Toxins / toxicity*
Phytoplankton / chemistry
Seafood / analysis*
Water Pollutants, Chemical / toxicity*
bcl-2-Associated X Protein / analysis,  metabolism
Reg. No./Substance:
0/Marine Toxins; 0/Water Pollutants, Chemical; 0/bcl-2-Associated X Protein; 14277-97-5/domoic acid; 487-79-6/Kainic Acid

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