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Nitrogen Intake and Tumorigenesis in Rats Injected with 1,2-Dimethylhydrazine^1,2,

Department of Animal Science, Cornell University, Ithaca, N.Y. 14850

Tumor incidence was studied in 1,2-dimethylhydrazine (DMH) injected male rats assigned at weaning to isoenergetic caseinsucrose diets containing 7.5%, 15%, or 22.5% protein with or without 2.5% urea. Twenty rats fed each diet were given weekly intraperitoneal injections of DMH (15 mg/kg body weight/week) for the first 24 weeks and 20 were given saline. Of 96 DMH-injected rats necropsied after 28 weeks, 88 were necropsied during the 32nd or final week of the experiment. Adenocarcinomas of the small and large intestine were larger and significantly more numerous in rats fed 15% and 22.5% dietary protein. Keratin producing papillomas of the sebaceous glands of the external ear were observed first at 21 weeks in DMH-injected rats fed 22.5% protein. These were subsequently observed in some rats from all DMH-treated groups. As time progressed, the ear tumors increased in size and number in all groups but the greatest incidence was in the group fed 22.5% protein. No tumors were observed in saline-injected rats. Urea feeding did not increase the number of tumors nor cause changes in pH, urease activity or ammonia concentration of contents of the colon or cecum, or blood cholesterol. As dietary protein increased, cecal ammonia concentrations rose while both colon and cecal pH dropped. Portal blood urea and cholesterol rose as dietary protein was increased. DMH-treated rats had significantly higher concentrations of colon and cecal ammonia and lower blood cholesterol. Although the rats fed 7.5% protein gained significantly less weight during 0 to 6 weeks of feeding, their weight gain was significantly higher during 6 to 26 weeks. No tumors were found in rats necropsied at 16 weeks.

KEY WORDS: • colonic cancer • small intestinal cancer • ear tumors • 1,2-dimethylhydrazine • ammonia • intestinal pH • blood cholesterol • dietary protein • dietary urea

¹ This research was conducted while Douglas C. Topping was a National Science Foundation Predoctoral Fellow. A detailed report is included in "Studies on the effect of ammonia and dietary nitrogen on replicative processes in the intestinal mucosa of the chick and the rat" presented as a thesis to the faculty of the Graduate School of Cornell University for the degree of Doctor of Philosophy, 1975. The results in preliminary form were reported in Topping, D. C. & Visek, W. J., Federation Proc. 35, 498 (Abs). 1976. Partial financial support was provided by US/PHS Grant FDO710.

² Reprint requests should be submitted to W. J. Visek.

³ Present address: Biology Division, Oak Ridge National Laboratory, P.O. Box Y, Oak Ridge, Tennessee 37830.

⁴ Present address: School of Basic Medical Sciences at Urbana-Champaign, University of Illinois, Urbana, Illinois 61801.

Manuscript received 22 March 1976.