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Promotion of Azoxymethane-induced Colonic Neoplasia by Resection of the Proximal Small Bowel¹

Surgical Services, Shriners Burns Institute, Massachusetts General Hospital, and Department of Surgery, Harvard Medical School, Boston, Massachusetts 02114

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 to 18 weeks (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 to 76%) and DNA (68 to 95%), taller villi, deeper crypts, and luminal dilation (p < 0.05 to 0.001); however, the colon showed only patchy hyperplasia. When the combined effects of azoxymethane and PSBR were observed 26 to 30 weeks after the first injection, rats with PSBR had an increased number of colonic tumors per animal (2.9 versus 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 to the promoting factor (PSBR).

¹ Supported by the USPHS through the National Cancer Institute and the National Large Bowel Cancer Project, Grant CA 17324, and the Henry Greco Memorial Fund.

² Present address: Department of Surgery, Bristol Royal Infirmary, Bristol, England.

³ Present address: Department of Surgery, University of Rotterdam, Rotterdam, The Netherlands.

⁴ Present address: Department of Surgery, University of Lund, Lund, Sweden.

⁵ Present address: Department of Pathology, Berkshire Medical Center, Pittsfield, Massachusetts 01201.

⁶ To whom requests for reprints should be addressed, at Massachusetts General Hospital, Boston, Mass. 02114.

Received 2/16/78. Accepted 6/23/78.

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