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Ornithine Decarboxylase Activity in the Rat and Human Colon¹

Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan 48201

We have investigated the effect of age, a high-fat diet, sodium deoxycholate, and the ornithine analogue -difluoromethylornithine on ornithine decarboxylase (ODC) activity in the rat colon. The relative levels of ODC activity were also determined in normal mucosa and tumor tissue from rat and human colon.

The colonic ODC activity induced by intrarectal instillation of sodium deoxycholate in male Sprague-Dawley rats was highest in young animals, and it decreased with increasing age. A high level of dietary fat caused both an increase in basal colonic ODC activity and enhanced ODC induction by deoxycholate. -Difluoromethylornithine given in drinking water inhibited, in a dose-dependent fashion, deoxycholate-induced ODC activity. The frequency of azoxymethane-induced intestinal tumors was also significantly reduced by -difluoromethylornithine.

Since colonic ODC activity is increased in carcinogenesis by known promoting agents and decreased by tumor inhibitors, this short-term assay may provide a useful system for identifying colon tumor promoters and inhibitors. The ODC activity in colon tumors of Sprague-Dawley rats was found to be significantly higher than in normal-appearing mucosa in the same animals. Similarly, ODC activity in human colon cancer was found to be higher than that of the normal-appearing mucosa in the same specimen. These results strengthen the utilization of the rat model for studies, the results of which may apply to the human situation.

¹ Supported by the Matilda R. Wilson Fund, the James and Lynelle Holden Fund, and individual private contributions. Reported in part at the National Large Bowel Cancer Project Workshop, Houston, TX, June 1983.

² To whom requests for reprints should be addressed, at Department of Surgery, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI.

Received 4/19/83. Accepted 4/26/84.

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