Modification of gastrointestinal tumor development in rats by dietary butylated hydroxytoluene

Male Fischer 344 rats were given two or four injections of 1,2-dimethylhydrazine (DMH), 40 mg/kg sc, and then fed a diet containing 0.5% butylated hydroxytoluene (BHT). Five months later, the animals treated with two doses of DMH had a significantly higher incidence of colon tumors than the animals fed a BHT-free control diet. In animals treated with four injections of DMH, the increase in colon tumor incidence was statistically not significant, but BHT appeared to produce a shift in tumor distribution. In a second experiment, Fischer 344 rats were treated with 2 X 40 mg/kg of DMH and fed a diet of 0.5 or 0.1% BHT for 6 months; these animals had a significantly increased incidence of small intestinal tumors (duodenum, jejunum, and ileum) compared with animals fed the control diet. In rats treated with DMH and given a diet of 0.5% butylated hydroxyanisole (BHA), overall incidence of gastrointestinal tract tumors was higher than in control animals, although the difference was statistically not significant. Administration of N-nitroso-N-methylurea (NMU; 90 mg/kg given orally) produced stomach and colon tumors; 0.5% BHT in the diet did not modulate tumor incidence. It is concluded that dietary BHT may enhance development of gastrointestinal tumors produced by DMH, but not by NMU, provided exposure to BHT occurs after exposure to the carcinogen.