The cytotoxicity and genotoxicity of okadaic acid are cell-line dependent
Autor: | Théophile A. Mobio, Serge Moukha, Edmond Ekoue Creppy, Ghada Souid-Mensi, Khira Maaroufi |
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Přispěvatelé: | Université de Bordeaux Ségalen [Bordeaux 2], Université de Monastir (Université de Monastir), Unité de recherche Mycologie et Sécurité des Aliments (MycSA), Institut National de la Recherche Agronomique (INRA) |
Rok vydání: | 2008 |
Předmět: |
DNA Repair
Apoptosis 010501 environmental sciences Toxicology medicine.disease_cause 01 natural sciences chemistry.chemical_compound DOK DNA DAMAGE REPAIR CYTOTOXICITY ACIDE OKADOÏQUE 0303 health sciences Caspase 3 Cytotoxins Base excision repair 3. Good health DINOFLAGELLES Biochemistry [SDV.TOX]Life Sciences [q-bio]/Toxicology C6 GLIOMA 3D NEUTRAL RED TEST Programmed cell death CACO2 DNA damage DNA repair Biology Cell Line HEPG2 03 medical and health sciences Okadaic Acid medicine Humans Cell Proliferation 030304 developmental biology 0105 earth and related environmental sciences L-Lactate Dehydrogenase Mutagenicity Tests Cell Membrane CELLULE CACO-2 Okadaic acid Molecular biology Enzyme Activation chemistry TOXINE MARINE Genotoxicity DNA Damage Mutagens Nucleotide excision repair |
Zdroj: | Toxicon Toxicon, Elsevier, 2008, 51 (8), pp.1338-1344. ⟨10.1016/j.toxicon.2008.03.002⟩ |
ISSN: | 0041-0101 |
Popis: | International audience; Okadaic acid (OA) is a polyether fatty acid produced mainly by dinoflagellates causing diarrhoeic shellfish poisoning (DSP) in humans. To resolve the controversies concerning its genotoxicity in vitro, we have investigated eventual specific cellular response in DOK, Caco-2 (Δp53/p53−), HepG-2 and C6 glioma cells using the DNA damage detection test (3d DNA repair test: nucleotide excision repair (NER) and base excision repair (BER)), caspase-3-triggered apoptosis, neutral red (NR) and lactate dehydrogenase (LDH) release tests. At low concentrations of OA (10 nM), cytotoxicity measured by LDH release is more marked in DOK cells, indicating necrotic cell death that occurs only slightly in HepG-2 cells. At the same concentration, caspase-3 activation-dependent apoptosis and DNA damage caused by OA were only detected in HepG-2 cells. This apoptosis appears to be p53 gene dependent. Cell death occurs in the other cell types only by necrosis at OA concentrations amended to cultures. Among the tested cell lines, HepG-2 cells are the most sensitive to OA (10–50 nM) at 12 and 72 h as revealed by the NR test. The 3D test shows that only HepG-2 cells bear damaged DNA at tested concentrations. It is concluded that the genotoxicity of OA is chiefly cell type dependent and concentration dependent, giving sense to controversial genotoxicity data found in the literature. |
Databáze: | OpenAIRE |
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