Drug-induced hypergastrinemia: absence of trophic effects on colonic carcinoma in rats.
OBJECTIVE
Published studies suggest that hypergastrinemia stimulates growth of normal or malignant colon tissue. Other studies dispute these findings. This study was designed to test the hypothesis that hypergastrinemia enhances progression or invasiveness of colon cancer.


METHODS
Colonic carcinomas were induced in male Sprague-Dawley rats by six weekly intraperitoneal injections of methylazoxymethanol. Four weeks after the last injection of carcinogen, the animals were randomized into four treatment groups, including vehicle control, low- and high-dose omeprazole, and ranitidine. After 10 weeks of treatment, the animals were bled, stomach weights were recorded, and colon tumors were mapped, enumerated, measured, and scored histopathologically by Dukes' classification. Crypt and mucosal heights were determined in colonic mucosa unaffected by tumor.


RESULTS
Drug administration induced a sustained hypergastrinemia that did not enhance tumor burden or invasiveness or crypt height/mucosal height ratios. Ranitidine-treated rats consumed less food, weighed less, and developed fewer tumors. This group also had lower crypt and mucosal heights than rats in the vehicle- or omeprazole-treated rats.


CONCLUSIONS
The results suggest that endogenous hypergastrinemia induced by these acid-suppressing drugs has no stimulatory effect on colon mucosal growth or progression or biological behavior of experimental rat colon cancer.
Pinson
D M
DM
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City.
Havu
N
N
Sztern
M I
MI
Mattsson
H
H
Looney
G A
GA
Kimler
B F
BF
Hurwitz
A
A
D000704:Analysis of Variance; D000818:Animals; D003110:Colonic Neoplasms / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D005755:Gastrins / Q000097:blood*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives; D009361:Neoplasm Invasiveness; D009853:Omeprazole / Q000009:adverse effects*; D011897:Random Allocation; D011899:Ranitidine / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005755:Gastrins; D008746:Methylazoxymethanol Acetate; D011899:Ranitidine; C030667:methylazoxymethanol; D009853:Omeprazole