THE IMPORTANCE OF SPONTANEOUS AND RADIATION INDUCED APOPTOSIS FOR STEM CELLS IN THE GASTROINTESTINAL TRACT

摘要

Apoptosis occurs at a low level in healthy unirradiated mice and also in humans. This spontaneous apoptosis is associated with cells in the stem cell region of the crypts of the small intestine. It is p53-independent and is assumed to be associated with the stem cell homeostatic processes. It is rare in the large intestine, probably because of the action of bcl-2. Radiation increases the levels of apoptosis at the stem cell location; peak levels are observed within 3-6 hours and the 6 cells in each crypt that appear to be susceptible to this mode of death are exquisitely radiosensitive. Other cells are reproductively sterilised and these have a greater resistance to radiation and are interpreted to be the clonogenic stem cell compartment. The apoptosis susceptible cells are interpreted to represent the ultimate stem cells which generate the clonogenic compartment by division. The radiation-induced apoptosis is an efficient protective mechanism, possibly accounting for the low cancer incidence figures in the small intestine. This protective mechanism is acting less efficiently in the large bowel, again because of the action of bcl-2.