SELENIUM AND DIFLUOROMETHYLORNITHINE ADDITIVELY INHIBIT DMH-INDUCED DISTAL COLON-TUMOR FORMATION IN RATS FED A FIBER-FREE DIET

We investigated the effects of difluoromethylornithine, an inhibitor of ornithine decarboxylase (ODC) and selenium supplementation on tumor formation induced by the carcinogen 1,2-dimethylhydrazine (DMH) in Sprague - Dawley rats. A biochemical link between polyamine biosynthesis and selenium metabolism to its cancer preventative form has been suggested by the common requirement of S-adenosylmethionine. One-hundred and twenty male Sprague-Dawley rats were divided into experimental (n = 80) and control (n = 40) groups. Experimental animals received DMH 20 mg/kg s.c. for 20 weeks. Animals were fed either a regular diet (selenium content 0.2 p.p.m.) or a high selenium diet (5 p.p.m.) with or without 0.2% DFMO in the drinking water. At death, week 30, animal weights within experimental or control groups were not different between the four diet treatment groups. Tumor number and incidence in the proximal colon was not affected by DFMO treatment, selenium supplementation or the combined treatment. In contrast, in the distal colon, 19 tumors developed in the DFMO treated group, 22 tumors in the high selenium group and only 12 tumors in the combined high selenium/DFMO treatment group compared to 32 tumors in the regular diet group. Similarly, tumor incidence was decreased by DFMO and selenium supplementation and their effects were additive. In control animals, ODC activity was decreased by DFMO treatment and selenium supplementation in the distal colon and liver, but not the proximal colon. ODC activity of tumor tissue was greater than normal colon tissue from diet paired animals for proximal and distal colon, except for distal colonic tumors in the high selenium/DFMO treatment group. Polyamine content, however, did not correlate with ODC activity in normal or neoplastic tissue. In general, S-adenosylmethionine levels from normal colon and liver tissue were unaffected by diet treatment. Selenium supplementation in combination with DFMO treatment selectively inhibited distal colon tumor formation in rats fed a fiber-free diet.