Studies of the mechanism of glucocorticoid-induced pyknosis in isolated rat thymocytes.

The lethal action of glucocorticoids on rat thymocytes in vitro is associated with the progressive accumulation of cells that display a discrete reduction in size. Techniques for the separation and quantitation of these structurally transformed cells have now been used to investigate the relationship between cell size changes and the effects of dexamethasone treatment on chromatin condensation and DNA fragmentation. The steroid-induced reduction in thymocyte size was invariably and exclusively associated with morphologically evident chromatin condensation and with fragmentation of DNA into units that were acid-precipitable but failed to sediment on low-speed centrifugation. The generation of cells of reduced size in response to dexamethasone was inhibited by actinomycin D, cordycepin and cycloheximide; the kinetics of inhibition indicate that glucocorticoid-induced cell death depends on the synthesis, processing and translation of mRNA coding for a protein or proteins whose subsequent lethal effect is expressed in a stochastic manner.