Cell death: questions for histochemists concerning the causes of the various cytological changes.

The question of cell death is accessible to study by histochemists and many questions remain to be resolved. From a physiological point of view, the most important are the causal relationships. (1) At what phase in cell death is the synthesis of RNA disrupted and at what phase is the rate of degradation of RNA increased? (2) Does the disruption of synthesis result from a direct genetic command, or does it result indirectly from gradual deterioration of energy resources or optimal ionic conditions? (3) What properties, presumably of the substrate organelles, marks them for specific absorption into autophagic vacuoles? (4) What proteases and other hydrolases operate currently undetected in the cytoplasm? How are they controlled and regulated? (5) Why does the physiologically dying cell shrink and appear more dense? To what extent is a cell in this state able to regulate any metabolic parameter? The advent of newer, more sensitive and quantitative techniques, and greater attention to the controls and causes as opposed to the phenomena, should help to resolve these questions.