Increase of labeling indices in gastrointestinal mucosae of mice and rats by compounds of the okadaic acid type

Abstract

Effects of compounds of the okadaic acid type (okadaic acid, dinophysistoxin-1, calyculin A and tautomycin) on proliferation by digestive-tract epithelial cells were investigated in mice and rats. In mice, a single oral administration of these agents caused significant enhancement of BrdU labeling indices in a dose/response manner. Exceptions showing no response were limited to the pyloric mucosa for okadaic acid, the pyloric and fundic mucosa for calyculin A and the pyloric mucosa for tautomycin. Sequential analysis of labeling indices after a single oral administration of dinophysistoxin-1 revealed two peaks of cell proliferation at 18 h and 36 h in the esophagus, ileum and colon. The labeling indices of the forestomach, fundus, pylorus and jejunum, on the other hand, continuously increased from 6 h after the administration. Elevated proliferation was also observed in the skin after 30 h or after, but no effects on the liver or kidney were evident. A single oral administration of the okadaic acid type of compounds also dose-dependently enhanced cell proliferation of the rat digestive tract. These results strongly suggest that the okadaic acid class of compounds may exert promoting potential for the gastrointestinal mucosa when administered orally.