HYPERGASTRINEMIA IN RATS WITH AZOXYMETHANE-INDUCED COLON CANCERS

Gastrin has been suggested to be involved in the promotion and progres sion of colon cancer. Mice colon cancers and colon-carcinoma cell line s are stimulated to grow by gastrin, and gastrin receptors have been f ound in the majority of human colon-tumor specimens. High serum gastri n levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in v itro it has been suggested that increased synthesis of intracellular p olyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to inv estigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possib le bias of human studies, related to varying diet, age and environment al factors, We evaluated blood gastrin levels in 35 rats with colon ca ncer induced by the carcinogen azoxymethane (AOM), and we correlated g astrinemia with tumor proliferation, assessed by thymidine-labeling in dex (TLI) and ODC activity; 6 animals constituted the control group. G astrin levels in rats with AOM-induced tumors were significantly highe r than in controls. Significantly higher TLI and ODC activity were fou nd in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells. (C) 1 995 Wiley-Liss, Inc.