DETECTING MEMBRANE IMPAIRMENT CAUSED BY XENOBIOTICS

The toxicity of 14 substituted anilines and 15 aliphatic alcohols was assessed by the electrorotation of yeast cells. Depending on the appli ed frequency, control cells exhibit both anti- and cofield rotation. F rom this spectrum, a frequency was selected at which untreated cells d o not rotate, but impaired cells rotate with the field. The experiment al spectra are fully in accord with theoretical models of the rotation al response, calculated on the basis of changes in membrane permeabili ty. High correlations exist between rotational data and physiological and biochemical end points (growth rate, plasma membrane ATPase, purin e transport of yeast cells, and antihemolytic assays with human erythr ocytes). A Quantitative Structure-Activity Relationship analysis was m ade, whereby rotation data from 23 phenols were included. The effects of all chemicals on cell rotation could be predicted by their lipophil icity. Some residuals and deviations could be accounted for by the inc lusion of molecular weight or connectivity in the analysis. 4-Nitrophe nol was an outlier, having an effect at least one order of magnitude h igher than predicted, suggesting a specific toxic mechanism. Based on lipophilicity and rotation data, the antihemolytic effect on erythrocy tes could be accurately estimated.