Alternating proliferative capacity in the rat gastrointestinal mucosa. Effects of E2 prostaglandins and indomethacin.

Abstract

Having previously observed an apparent uneven distribution of proliferating cells in the gastric corporic mucosa of the rat, we examined the mitotic distribution along 8-mm sections of gastric and jejunal epithelia. Metaphases were arrested with vincristine to facilitate mitotic count, and the effects of treatment with a prostaglandin E2 analogue and a cyclooxygenase blocker were examined. Clusters of mitotic figures alternating with non-proliferating areas were observed in the gastric corporic epithelium of control rats. During 4 h mitotic activity was absent over 21% of the corporic mucosa. Extending the examined area to about 240 glands reduced substantially the error of mitotic counts. An uneven distribution of mitoses was found in the antral and jejunal epithelium, but areas without proliferating cells were uncommon. Treatment with the prostaglandin E2 analogue reduced the number of mitosis-free areas in the gastric corpus to 13%, and clusters were less easily identified. The total mitotic count was unaffected by treatment. In the jejunum prostaglandin increased the absolute number of mitoses. The mitotic span was also increased, reflecting the uneven distribution. Indomethacin produced the opposite effects to the prostaglandin analogue, including reduction of epithelial height. Of the gastric corporic mucosa 35% was non-proliferating during the observation period, but the clustering phenomenon was still apparent. Absence of dose relationship was attributed to ulcerogenic actions of high doses of indomethacin. It is concluded that mitoses are unevenly distributed in the upper gastrointestinal epithelium of the rat and that safe estimates of mitotic count require examination of large corporic areas.(ABSTRACT TRUNCATED AT 250 WORDS)