Assessment of cellular and molecular toxicity by in vitro tests: The okadaic acid toxin case

The toxicological evaluation of chemical substances at the cellular and molecular level requires the application of a battery of in vitro tests in order to perform a detailed characterization of the whole spectra of effects. In order to illustrate this with a practical example the assessment of in vitro toxicity caused by the marine toxin okadaic acid (OA) is described in this chapter. OA is the main representative toxin responsible for diarrheic shellfish poisoning (DSP) caused by consumption of shellfish and other marine organisms. However, results of several studies suggest that this toxin could also be an important threat to public health even at concentrations below the limits established by the current regulation. Hence, we evaluated the toxic effects induced by OA in different human cells (leucocytes, neurons and hepatocytes), in order to determine the potential human risk related to the exposure to this toxin. The characterization of OA toxicity was carried out at different levels, ranging from genotoxicity and cytotoxicity to alterations in DNA repair processes and changes in gene expression patterns. A wide variety of techniques and experimental conditions were employed with this aim. The results obtained from these experiments showed that OA induces cytotoxic and genotoxic effects, including alterations in DNA repair processes, in all the cells evaluated though these effects are highly dependent on cell type, OA dose, exposure time, and presence of metabolic activation. Furthermore, the expression of a number of genes with differentrelevant cell functions was found to be altered after OA exposure, suggesting a possible molecular basis for most cellular effects previously observed.