GAMMA-RAY-INDUCED TRANSCRIPTION AND APOPTOSIS-ASSOCIATED LOSS OF 28S RIBOSOMAL-RNA IN INTERPHASE HUMAN-LYMPHOCYTES

Apoptosis, related to a naturally-occurring or programmed cellular dea th process, can be physiologically or exogenously induced. In vertebra te cells undergoing apoptosis, initiated by any of these ways, one of the numerous biochemical changes is an endogenous endonuclease activat ion that cleaves the chromatin DNA into oligonucleosome-sized 'ladder' fragments. In the present study we show that in parallel to chromatin DNA cleavage, ribosomal RNA is lost in gamma-ray-mediated apoptotic h uman lymphocytes. We demonstrate that 28S rRNA gene transcription is i nduced early (15 min) after irradiation, followed by a selective disap pearance in apoptotic cells only. The fact that newly synthesized rRNA turns over at the same rate in irradiated and untreated cell fraction s, highly suggests that the observed loss of 28S rRNA in the apoptotic cell fraction at the ribosome level is due to degradation occurring a t a late stage of the apoptotic death process. These results suggest t hat, in addition to first-stage apoptosis-associated rDNA gene activat ion, cellular self-destruction at late stages is associated with proce sses occurring simultaneously at the ribosome level involving an endog enous RNase-like activity, and at the chromatin level involving DNA-nu clease activity.