ToxSci Advance Access published online on May 12, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh139
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 Biochemistry and Molecular Biology Department, University of Oviedo, Oviedo, Spain
* To whom correspondence should be addressed. E-mail: neurolab{at}bioquimica.uniovi.es.
Diarrhetic Shellfish Poisoning (DSP) toxins of algal origin are frequent contaminants of coastal waters and seafood. The potential risk for human health due to the continuous presence of these toxins in food has not been clearly established. We have used cerebellar primary cultures to investigate the effects of the DSP toxin dinophysistoxin-2 (DTX-2) on central nervous system neurons and glial cells. Exposure to DTX-2 produced neurotoxicity at concentrations starting at 2.5 nM, characterized first by disintegration of neurites and later by cell death. DTX-2-induced neurodegeneration required long exposures (at least 20 h), involved DNA fragmentation and condensation and fragmentation of chromatin, typical hallmarks of apoptosis, and required the synthesis of new proteins. The concentration that reduced by 50% the maximum neuronal survival after 24h exposure to DTX-2 (EC5024) was
Accepted March 26, 2004
Neurotoxicology
The Marine Toxin Dinophysistoxin-2 Induces Differential Apoptotic Death of Rat Cerebellar Neurons and Astrocytes
2 PROTEOBIO, Mass Spectrometry Center for Proteomics and Biotoxin Research, Department of Chemistry, Cork Institute of Technology, Bishopstown, Cork, Ireland
3 Biochemistry and Molecular Biology Department, University of Oviedo, Oviedo, Spain; Psychology Department, University of Oviedo, Oviedo, Spain
Abstract 
8nM. Morphology and viability of glial cells remained unaffected up to at least 15nM DTX-2. Higher concentrations of the toxin caused strong shrinkage of glial cell bodies and retraction of processes, and a significant reduction of glial cell viability. Glial toxicity by DTX-2 involved typical apoptotic condensation and fragmentation of chromatin. Compared to neurons, the effect on glial cells was a much shorter process, and extensive glial degeneration and death occurred after 7h exposure to DTX-2 (EC507 50nM; EC5024 30 nM). Although further experiments are needed to confirm these toxic actions "in vivo", our "in vitro" data suggest that chronic exposure to amounts of DSP toxins below the current safety regulatory limits may represent a risk for human health that should be taken into consideration.
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