Effects of dietary administration of chenodeoxycholic acid on N-methyl- N-nitrosourea-induced colon cancer in rats

Abstract

This experiment examines the effects of chenodeoxycholic acid feeding on tumor incidence in rats treated with N-methyl- N-nitrosourea. Group 1 rats received control chow, group 2 control chow plus chenodeoxycholic acid (0.2%), group 3 control chow and N-methyl- N-nitrosourea, and group 4 control chow plus chenodeoxycholic acid (0.2%) and N-methyl- N-nitrosourea. After 28 weeks pathological and histological examination revealed no tumors in group 1 and group 2 rats. The N-methyl- N-nitrosourea group (group 3) had a tumor incidence of 49% (1.1 tumors/all animals) compared to the N-methyl- N-nitrosourea and chenodeoxycholic acid group (group 4) in which 62% of the animals had tumors (1.1 tumors/all animals). The number of tumors per tumor-bearing animal was slightly lower in group 4. The tumors were primarily adenomas, but 3 carcinomas in situ and 9 invasive carcinomas were also detected. Fecal analyses after 28 weeks showed a slight increase in neutral sterols in the N-methyl- N-nitrosourea group compared to controls (2.49 vs. 1.52 mg/g, respectively). In addition, fecal neutral sterols were slightly elevated in the chenodeoxycholic acid fed rats (groups 2 and 4). Conversion of cholesterol to coprostanol was similar in all groups. Total fecal bile acids were higher in chenodeoxycholic acid fed rats compared to control chow fed rats (groups 2 and 4 vs. groups 1 and 3). Major fecal bile acids in the chenodeoxycholic fed rats were chenodeoxycholic acid, lithocholic acid, α-muricholic acid, β-muricholic acid and ω-muricholic acid. The ability of rats to 6-hydroxylate and 7-hydroxylate bile acids may protect them from the increased tumor incidence observed in other carcinogen-bile acid experiments.