Inhibition of diphtheria toxin degradation and cytotoxic action by chloroquine.

Chloroquine was found to prevent the cytotoxic action of diphtheria toxin on cultured monkey kidney cells. Analysis of the cellular processing of 125I-labeled diphtheria toxin showed that chloroquine does not affect the rate or extent of toxin uptake but substantially blocks degradation. These studies provide strong evidence that diphtheria toxin enters monkey kidney cells primarily by adsorptive endocytosis and suggest that lysosomal processing is involved in intracellular activation of the proenzyme form of the toxin.