Synergistic effects of some metals contaminating mussels on the cytotoxicity of the marine toxin okadaic acid

Okadaic acid (OA), a marine toxin is cytotoxic and promotes tumours in mous e skin. It is a specific and potent inhibitor of protein synthesis and also inhibits phosphatases A1 and A2 in vitro. In the present study, we investi gated the influence of metals found at acceptable levels in mussels as envi ronmental pollutants on the cytotoxicity of OA in Vero cells. Among the met als found in mussels (Mytilus edulis), the most represented, in terms of mo lar quantities per gram of dried weight are aluminium (230 nmol/g), copper (58 nmol/g), lead (16 nmol/g), mercury (14 nmol/g) and cadmium (7.4 nmol/g) . A solution containing these five metals Al3+, Cu2+, Pb2+, Hg2+ and Cd2+ c ombined at the concentrations detected in mussels, stimulated protein synth esis (+25%, P < 0.01), whereas different dilutions of this solution in the presence of okadaic acid (15 ng/ml, i.e. 18.7 x 10(-9) M) increased the per centage of protein synthesis inhibition from 35 to 79%. The metals also inc reased the lactate dehydrogenase (LDH) release into the medium and the lipi d peroxidation induced by this algal toxin. In addition, these metals reduc ed the cell viability for an incubation period of 24 h especially at the tw o higher concentrations. These results indicate that metals (Al3+ Cu2+, Pb2 +, Hg2+, Cd2+) in concentration ranges largely below the acceptable levels, synergistically increase the cytotoxicity of low concentrations of OA in c ultured cells.