Regulation of apoptotic cell death in the pyloric glands of the canine stomach

In gastrointestinal epithelia, apoptosis has been thought to play a part in the shedding of postmitotic cells into the lumen. However, we have found that apoptosis more frequently in the generative cell (G) zone (the lower one third of the pit) than in the luminal zone (the upper one third of the pit) and the gland zone in the canine pyloric gland. To analyse the regulation of apoptotic cell death in each zone, we labelled S-phase cells by single and repeated injections of bromodeoxyuridine (BrdU) IV at intervals of 8 h. We found that 30% of apoptoses in the G zone were flash-labelled by BrdU and might derive from cells in or just after the S phase. The incidence of apoptosis and mitotic index did not change significantly after repeated injections of BrdU until the 49-h point, when the incidence of apoptosis increased and the mitotic index decreased significantly in the G zone, while the incidence of apoptosis decreased in the luminal zone. The BrdU-induced increase of apoptosis and cell-cycle arrest at the 49-h point may be caused by enhanced DNA mispairs that are elicited by incorporation of BrdU, in particular using the template of BrdU incorporated DNA. Apoptosis in the luminal zone may be down-regulated by reduced cell production in the G-zone.