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Okadaic acid induces morphological changes, apoptosis and cell cycle alterations in different human cell types
Vanessa Valdiglesias1, Blanca Laffon, Eduardo Pásaro
1Toxicology Unit, Psychobiology Department, University of A Coruña, Edificio de Servicios Centrales de Investigación, Campus Elviña s/n, 15071 A Coruña, Spain.
Journal of Environmental Monitoring : JEM
|April 29, 2011
Summary
Okadaic acid (OA), a marine toxin found in shellfish, causes cell damage and triggers apoptosis in human cells like leukocytes and neurons. Metabolic activation by the S9 fraction appears to detoxify OA, preventing apoptosis.
Area of Science:
- Marine Toxinology
- Cell Biology
- Toxicology
Background:
- Okadaic acid (OA) is a marine toxin from dinoflagellates, accumulating in seafood.
- OA's precise mechanism of action and toxicological effects remain unclear, with conflicting research findings.
- Understanding OA's impact on human cells is crucial due to dietary exposure risks.
Purpose of the Study:
- To investigate the effects of Okadaic acid (OA) on human cell morphology, cell cycle progression, and apoptosis.
- To compare OA's toxicity across different human cell types: leukocytes, HepG2 cells, and SHSY5Y cells.
- To evaluate the role of metabolic activation (S9 fraction) in OA's toxicological profile.
Main Methods:
- Exposure of human leukocytes, HepG2, and SHSY5Y cells to varying concentrations of OA.
- Morphological assessment using light microscopy.
- Cell cycle analysis and apoptosis detection via flow cytometry, caspase 3 activation assays, and annexin V staining.
Main Results:
- OA induced significant morphological alterations in all tested human cell types.
- Cell cycle disruption was observed in leukocytes and SHSY5Y (neuronal) cells, with SHSY5Y cells being most sensitive.
- OA treatment led to increased apoptosis in all cell types without S9 fraction, indicating a caspase 3-dependent pathway. In contrast, the S9 fraction reduced OA-induced apoptosis, suggesting metabolic detoxification, though necrosis occurred in neuroblastoma cells.
Conclusions:
- Okadaic acid exerts direct cytotoxic effects, inducing apoptosis in various human cell types.
- Metabolic activation, potentially via the S9 fraction, plays a role in detoxifying OA, mitigating its apoptotic effects.
- SHSY5Y cells exhibit higher sensitivity to OA, highlighting potential neurotoxic risks.
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