Increase of labeling indices in gastrointestinal mucosae of mice and rats by compounds of the okadaic acid type
- 27 Downloads
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.
Key wordsOkadaic aicd Digestive tract Gastrointestinal mucosae Cell proliferation Protein phosphatases 1, 2A
Unable to display preview. Download preview PDF.
- Edebo L, Lange S, Li XP, Allenmark S, Jennishe E (1989) Diarrhetic shellfish toxins induce rapid swelling of the intestinal epithelium and hypersecretion in the rat small intestine. In: Natori S, Hashimoto K, Ueno Y (eds) Mycotoxins and phycotoxins. Elsevier: Amsterdam, pp 437–444Google Scholar
- Fabrikant JI (1967) The spatial distribution of parenchymal cell proliferation during regeneration of the liver. Johns Hopkins Med Bull 120:147–147Google Scholar
- Fujiki H, Suganuma M, Suguri H, Yoshizawa S, Takagi K, Uda N, Wakamatsu K, Yamada K, Murata M, Yasumoto T, Sugimura T (1988) Diarrhetic shellfish toxin, dinophysistoxin-1, is a potent tumor promoter on mouse skin. Jpn J Cancer Res (Gann) 79:1089–1093Google Scholar
- Murata M, Shimatani M, Sugitani H, Oshima Y, Yasumoto T (1982) Isolation and structure elucidation of the causative toxin of the diarrhetic shellfish poisoning. Bull Jpn Soc Sci Fish 48:549–552Google Scholar
- Pardee AB, Coppock DL, Yang HC (1986) Regulation of cell proliferation at the onset of DNA synthesis. J Cell Sci Suppl 4:171–180Google Scholar