Phenotypic yeast growth analysis for chronic toxicity testing

In Saccharomyces cerevisiae the pH-dependent growth inhibition of the heavy metals Cu 2+, Cr6+, Zn2+, Co2+, and Cd2+ was examined in comparison to that of organic solvents and pure compounds DMSO, MNNG, 4-NQO, MTBE, ethanol, and 2-AA. The assay was based on both S. cerevisiae wild-type and genetically modified cells deleted in the transporters Pdr5, Snq2, and Yor1 that facilitate pleiotropic drug resistance to explore the potential for short-term chronic aquatic toxicity tests. The strain deleted in the proteins that mediate the efflux of structurally diverse hydrophobic compounds exhibited high sensitive growth inhibition at low (0.04 mg/L 4-NQO) to moderate (5.5 mg/L DMSO) organic compound exposure. At pH 6.4 the EC50ʹs, for all tested heavy metals were significantly low, in contrast to acidic pH conditions, in which both strains were able to grow in the presence of high concentrations of the transition metals Cu2+, Zn2+, and Co2+, with the pdr5 yor1 snq2 mutant being more tolerant. Cd2+ exerted the highest toxicity, with an EC50 of 0.49 mg/L. Obtained results were compared with data determined from growth-inhibition tests involving other unicellular species. The comparison provided evidence that yeast is a sensitive and practical model system for toxicological risk assessment.