Effects of PR toxin on liver cells in culture

We studied the effects on liver cells in culture of PR toxin, a substance produced from Penicillium roqueforti. PR toxin displayed cytotoxicity which increased as a function of its concentration but the form of such toxicity differed, depending on the toxin's concentration. Thus, cells only underwent quick retraction and intensive vacuolization when treated with low drug concentrations, and they came away from the substrate easily under these conditions. By contrast, the major events observed in the case of high concentrations were loss of structure of the nuclei and strong adhesiveness of dead cells to the support. PR toxin already inhibited cell multiplication at low concentrations and became toxic when the concentration was raised; growth inhibition decreased but the toxic effect increased when cells passed from the exponential growth phase to a phase of slower growth. PR toxin inhibited tritiated precursor incorporation into DNA, RNA and proteins in a similar time and concentration-dependent manner. Inhibition of DNA synthesis persisted even after removal of the drug from the medium.