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.