TIME-DEPENDENT CHANGES IN ENTEROCHROMAFFIN-LIKE CELL-KINETICS IN STOMACH OF HYPERGASTRINEMIC RATS

Background: Hypergastrinemia has been claimed to cause first hyperplasia and then dysplasia/neoplasia of enterochromaffinlike (ECL) cells in rat stomach. The growth is thought to reflect an accelerated self replication rate of mature ECL cells. The cytokinetics and the histidine decarboxylase (HDC) activity of the ECL cells were investigated during sustained hypergastrinemia. Methods: Hypergastrinemia was evoked by omeprazole (400 μmol · kg-1 · day-1 orally) for up to 1 year. Immunocytochemistry for histamine was used to determine the ECL cell density and combined with [H3]thymidine autoradiography to establish the labeling index (LI), i.e., the proportion of the ECL cells that has incorporated [H3]thymidine. Results: The ECL cell density increased progressively for 10-20 weeks in response to the hypergastrinemia and remained at a plateau for the remainder of the study. The hyperplasia was diffuse with additional micronodules at 52 weeks. The ECL cell LI was maximally elevated after 1-2 weeks and declined to control values after 10-20 weeks of treatment. In contrast, the HDC activity remained elevated for the duration of the study. Conclusions: The ECL cell hyperplasia reflects the transiently elevated ECL cell LI during the early phase but is not associated with an accelerated rate of mitosis during the 10-52 weeks period. Even though with time gastrin seems to loose its ability to sustain a high ECL cell LI it retains its ability to maintain a high HDC activity. © 1993.