Domoic acid induces direct DNA damage and apoptosis in Caco-2 cells: recent advances.
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.
Pinto-Silva
C R Carvalho
CR
Toxicology Department, UFR of Pharmaceutical Sciences, University of Bordeaux 2, France.
Moukha
S
S
Matias
W G
WG
Creppy
E E
EE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D005517:Foodborne Diseases; D019254:Genes, bcl-2 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008387:Marine Toxins / Q000633:toxicity*; D010839:Phytoplankton / Q000737:chemistry; D017747:Seafood / Q000032:analysis*; D012623:Seawater; D012758:Shellfish; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000378:metabolism
D008387:Marine Toxins; D014874:Water Pollutants, Chemical; D051028:bcl-2-Associated X Protein; C012301:domoic acid; D007608:Kainic Acid