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Title: Short term infusion of glycine-extended gastrin(17) stimulates both proliferation and formation of aberrant crypt foci in rat colonic mucosa.
Austin Authors: Aly, Ahmad ;Shulkes, Arthur;Baldwin, Graham S
Affiliation: University of Melbourne Department of Surgery, Austin Campus, A&RMC, Melbourne, Victoria, Australia
Issue Date: 1-Nov-2001
Publication information: International Journal of Cancer. Journal International Du Cancer; 94(3): 307-13
Abstract: Evidence is accumulating that gastrin precursors may act as growth factors for the colonic mucosa in vivo and for colorectal carcinoma cell lines in vitro. The effect of short term administration of synthetic gastrins on the colonic mucosa in vivo, however, has not been reported. The aim of our study was to determine whether continuous systemic infusion of glycine-extended gastrin(17) stimulated proliferation and accelerated carcinogenesis in the colorectal mucosa. A significant increase in colonic mucosal proliferation as assessed by metaphase index was seen in the caecum (23%, p < 0.02) and distal colon (27%, p < 0.001), but not the rectum, after treatment of intact rats with glycine-extended gastrin(17) for 1 week using implanted miniosmotic pumps. Defunctioning of the rectum reduced both the proliferative index and crypt height of the rectal mucosa of untreated rats. Treatment of rectally defunctioned animals with glycine-extended gastrin(17) for either 1 or 4 weeks resulted in a significant increase in both the proliferative index (40% and 93%, respectively) and crypt height (11% and 19%, respectively) of the rectal mucosa. The total number of aberrant crypt foci in intact rats treated with the procarcinogen azoxymethane plus glycine-extended gastrin(17) was increased by 48% compared to the value in controls treated with azoxymethane only (p = 0.01). We conclude that short term administration of glycine-extended gastrin(17) to mature rats not only has a proliferative effect upon colonic mucosa, but also increases the number of aberrant crypt foci formed in the colorectal mucosa after treatment with azoxymethane. Glycine-extended gastrin(17) could thus potentially act as a promoter of carcinogenesis.
Gov't Doc #: 11745407
Type: Journal Article
Subjects: Animals
Cell Division
Colon.drug effects.metabolism
Colonic Neoplasms.chemically induced
Mucous Membrane.drug effects.metabolism
Precancerous Conditions.chemically induced
Rats, Sprague-Dawley
Time Factors
Appears in Collections:Journal articles

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