PROMOTION OF AZOXYMETHANE-INDUCED COLONIC NEOPLASIA BY RESECTION OF PROXIMAL SMALL BOWEL

Abstract

Potential enhancement of intestinal neoplasia by compensatory mucosal hyperplasia was tested in rats subjected to 50% proximal small bowel resection (PSBR) 10 days after the last of 16 weekly injections of azoxymethane. Azoxymethane alone increased jejunal contents of RNA and DNA each by 26% at 17-18 wk (P < 0.01) before there was macroscopic evidence of neoplasia. Three months after PSBR alone, ileal hyperplasia was characterized by increased amounts of RNA (42-76%) and DNA (68-95%), taller villi, deeper crypts and luminal dilation (P < 0.05-0.001). The colon showed only patchy hyperplasia. When the combined effects of azoxymethane and PSBR were observed 26-30 wk after the 1st injection, rats with PSBR had an increased number of colonic tumors per animal (2.9 vs. 1.6 for controls; P < 0.02). Despite the intense ileal hyperplasia produced by PSBR, ileal neoplasia did not occur. Enhanced colonic carcinogenesis followed sequential exposure of the mucosa to the carcinogen (azoxymethane) and the promoting factor (PSBR).