Hypergastrinemia in rats with azoxymethane-induced colon cancers

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin 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 vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found 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.