In vitro and in vivo effects of exogenous nucleotides on the proliferation and maturation of intestinal epithelial cells.

To determine the nutritional role of nucleotides, the in vitro and in vivo effects of exogenous nucleotides on the development of intestine were investigated. First, the in vitro effects of nucleotides on the proliferation and maturation of enterocytes were studied by using a human colon tumor cell line (Caco-2) and a rat normal small intestinal crypt cell line (IEC-6). Second, the in vivo effects of nucleotides were also studied in early weaned rats fed nucleotide-unsupplemented or high-nucleotide-supplemented diet. Nucleotide composition resembled that of human milk (CMP:UMP:AMP:IMP:GMP = 10:1:1:1:1, in weight). Nucleotide supplement did not enhance Caco-2 cells proliferation; however, it significantly enhanced maltase and sucrase activities. In contrast, nucleotides supplement enhanced ICE-6 cells proliferation and maltase activity. CMP, predominantly contained in the mixture, enhanced most effectively the proliferation and maturation of cells. In the in vivo experiment, nucleotides significantly enhanced sucrase activity in the intestinal mucosa of early weaned rats. The results presented here suggest that a nucleotide supplement may enhance enterocyte proliferation and/or maturation in vivo and in vitro. Therefore exogenous nucleotides may play an important role in the development of the intestine.