Tumorigenic effects of direct- and indirect-acting chemical carcinogens in rats on a restricted diet.

The influence of diet restriction on induction of intestinal tumors in Sprague-Dawley rats by two unique carcinogenic agents was investigated: methylazoxymethanol acetate [(MAM) CAS: 592-62-1], which requires metabolic activation, and N-methylnitrosourea [(MNU) CAS: 684-93-5], which is a direct-acting carcinogen. Most of the tumors induced by MAM developed in the small intestine and less frequently in the colon, but MNU produced tumors predominantly in the colon. Among rats fed the restricted diet (12 g/day), the production of tumors by MAM was significantly reduced compared to that of counterpart rats on the ad libitum diet. However, dietary restriction did not modify the production of tumors in rats by MNU. The same relationship of diet restriction to tumor induction was demonstrable when MAM and MNU were administered to the same test rats: Numbers of MAM-related tumors, especially in the small intestine, were reduced and numbers of MNU-related tumors in the colon were unchanged. Dietary restriction modified the tumorigenic response of rats to MAM but not to MNU.