Cell kinetics of rat gastrointestinal mucosa. Autoradiographic study after treatment with 15(R)15-methyl-prostaglandin E2

Abstract

Forty Sprague Dawley rats (120 g) were divided in groups of five rats each, and 2 mg , kg-1 15(R)15-methyl-prostaglandin E2 or vehicle was administered orally, twice daily for 5 days. On the 6th day, 1 mCi . kg-1 methyl-3H-thymidine was given intraperitoneally to all rats. Groups of rats were killed at 45 min and 24 h, 72, and 120 h after the labelling. Treatments were continued until death. Samples were taken from the corpus, antrum, and jejunum and processed for autoradiography. Microscopic evaluation of the proliferative and functional compartments included cell counts and determination of the labelling index (LI) and mitotic index (MI). Prostaglandin treatment increased the number of cells in the jejunal and gastric epithelia. The DNA synthesis, evaluated from the LI and 45 min after thymidine injection, was unaffected by treatment. The clearance of label from jejunal crypts and villi was significantly slower in the prostaglandin groups. Similar observations were made in the proliferative zone of the corporal and antral epithelia. The MI was unchanged or reduced by prostaglandin treatment, the reduction being significant after 8 to 10 days' treatment. It is suggested that the trophic action of prostaglandin E2 is produced by reduction of epithelial cell losses, thereby prolonging the cell survival time. The reduced MI may be secondary to negative feedback from the hyperplastic epithelium. Trophic actions are produced by short-term treatments.