Effects of 1 alpha-hydroxyvitamin D3 on N-methyl-N-nitrosourea-induced colonic tumorigenesis, and on fecal bile acid profiles with respect to soluble and precipitated phases in rats.

Vitamin D3 inhibited the promotion by exogenous promoters in experimental colonic tumorigenesis. To give more insight into this phenomenon, the effect of 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) on N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis was studied in rats without exogenous promoters. Fecal bile acids were analyzed to examine as to whether 1 alpha(OH)D3 increased the concentration of soluble bile acids. Eighty-seven female F344 rats received 2 mg of MNU intrarectally 5 times in 2 weeks, and were divided into 3 groups. One group (n = 29) was left without any treatment. Two groups (each, n = 29) were given 0.2 ml of medium chain triglyceride (MCT) or MCT containing 0.04 microgram of 1 alpha(OH)D3 through an intragastric route thrice weekly for 38 weeks. At autopsy, numbers of rats with colonic tumor were 9 (31%), 10 (34%) and 10 (34%) in the group receiving MNU alone, MNU + MCT and MNU + 1 alpha(OH)D3, respectively (chi 2 = 0.103, P less than 0.95). Fecal bile acid profiles showed no appreciable difference among these groups, nor was observed any increase of soluble bile acids in the MNU + 1 alpha(OH)D3 group. These results indicated that the administration of 1 alpha(OH)D3 did not affect colonic tumorigenesis under the condition where exogenous promoters were not applied, and that 1 alpha(OH)D3 did not seem to interfere the formation of bile acid calcium salts in animals on a regular diet.