IN-VIVO TIME-COURSE OF MORPHOLOGICAL-CHANGES AND DNA-DEGRADATION DURING THE DEGENERATION OF CASTRATION-INDUCED APOPTOTIC PROSTATE CELLS

The in vivo time course of the morphological changes and DNA degradati on in castration-induced apoptotic prostate cells was studied from the earliest to the latest stage of the degeneration process. To study th is problem, we first induced apoptotic prostate cells in rats by castr ation for 3 days and then promptly and continuously blocked the death of healthy prostatic cells in the castrated rats by in vivo testostero ne replacement. Because testosterone replacement could not stop the ir reversible lysis of already damaged prostate cells, apoptotic cells at different stages of the degeneration process were eliminated sequenti ally from the prostate after the healthy prostate cells had been prote cted. Prostate cells at the earliest stage of apoptosis at the time wh en the castrated rats received testosterone replacement disappeared la st. By tracing the morphological and DNA degradation of apoptotic cell s after hormone treatment, we estimated the time course of prostate ce ll death from the early to the final stage. In the morphological evolu tion of apoptotic prostate cells, the clumping of nuclear chromatin, t he degeneration of cytoplasm and the involution of the cell surface oc curred and progressed simultaneously, resulting in the rapid formation of apoptotic bodies that were gradually digested by other cells. The DNA ladders of apoptotic cells were progressively cleaved into a monon ucleosomal subunit that was further degraded at an additional site, ge nerating a heterogeneous population of small nucleotides. The final di gestion of DNA fragments occurred within the apoptotic bodies. The who le course of prostate cell death after castration took about 44 h.