The cytotoxicity and genotoxicity of okadaic acid are cell-line dependent.
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 (Deltap53/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 (10nM), 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 (10-50nM) at 12 and 72h 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.
Laboratory of Toxicology and Applied Hygiene, University Victor Segalen Bordeaux, 146 rue Léo-Saignat, Bordeaux, France.
Ghada
G
Souid-Mensi
Serge
S
Moukha
Theophile A
TA
Mobio
Khira
K
Maaroufi
Edmond E
EE
Creppy
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D019319:Okadaic Acid / Q000633:toxicity*
D003603:Cytotoxins; D009153:Mutagens; D019319:Okadaic Acid; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3