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 degradation in castration-induced apoptotic prostate cells was studied from the earliest to the latest stage of the degeneration process. To study this problem, we first induced apoptotic prostate cells in rats by castration for 3 days and then promptly and continuously blocked the death of healthy prostatic cells in the castrated rats by in vivo testosterone replacement. Because testosterone replacement could not stop the irreversible lysis of already damaged prostate cells, apoptotic cells at different stages of the degeneration process were eliminated sequentially from the prostate after the healthy prostate cells had been protected. Prostate cells at the earliest stage of apoptosis at the time when the castrated rats received testosterone replacement disappeared last. By tracing the morphological and DNA degradation of apoptotic cells after hormone treatment, we estimated the time course of prostate cell death from the early to the final stage. In the morphological evolution of apoptotic prostate cells, the clumping of nuclear chromatin, the degeneration of cytoplasm and the involution of the cell surface occurred 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 mononucleosomal subunit that was further degraded at an additional site, generating a heterogeneous population of small nucleotides. The final digestion of DNA fragments occurred within the apoptotic bodies. The whole course of prostate cell death after castration took about 44 h.