Implication of okadaic acid on DNA adduct formation and EROD activity

Okadaic acid(OA), a marine toxin mainly involved in diarrheic shellfish poisoning (DSP) has been shown to be a potent tumor promoter in mouse skin and glandular stomach. Recent studies presented some evidence that OA can also act as a genotoxic compound. Moreover, no indication is available on its biotransformation. This study was therefore initiated to determine: whether DNA adduct formation will occur in two cell lines (BHK21 C13 fibroblasts and HESV keratinocytes) cultured for 24 hours in presence of OA, the ability of this toxin to activate hepatic xenobiotic metabolizing enzymes after intraperitoneal injection to the marine fish model Dicentrarchus labrax. Several DNA adducts were observed in OA treated BHK21 C13 and HESV cells. Ten adducts with similar Rf were detected in the two cell lines while 9 were specific for the BHK21 C13 cell line and 5 for HESV one. The highest total DNA adduct level was 95.6/10(9) normal nucleotides for BHK21 C13 fibroblasts treated with 1nM OA and 31.1/10(9) normal nucleotides for HESV keratinocytes (0.5nM). Moreover, injection of OA (0.5 and 1 mu g/fish) increased hepatic EROD activity (reflecting cup 1Al activity) whereas hepatic microsomal NADPH cytochrome C reductase and cytosolic glutathion-S-transferase activities were unchanged. A relationship between DNA adduct formation and activation of EROD by OA can be suggested.