NUCLEOTIDE SUPPLEMENTS ALTER PROLIFERATION AND DIFFERENTIATION OF CULTURED HUMAN (CACO-2) AND RAT (IEC-6) INTESTINAL EPITHELIAL-CELLS

The effect of exogenous nucleotides on the proliferation and different iation of enterocytes was comparatively studied using a human colon tu mor cell line (Caco-2) and a normal rat small intestinal crypt cell li ne (IEC-6). Caco-2 cells exhibited more active endogenous nucleic acid metabolism than did IEC-6 cells, as evidenced by greater cellular poo ls of nucleotides and their metabolites. To determine the supplemental nutritional effect of nucleotides, a mixture containing equal amounts (10 mg/L) of AMP, CMP, IMP, GMP and UMP was added to the culture medi um. The results showed that a nucleotide supplement under normal cultu re conditions did not affect proliferation and differentiation of Caco -2 cells. In contrast, nucleotide supplements under normal culture con ditions promoted proliferation of IEC6 cells. The addition of nucleoti des to the culture medium also enhanced differentiation of IEC-6 cells when grown on an extracellular matrix (Matrigel(TM)). Furthermore, wh en glutamine levels were less than optimal (nutritional stress conditi ons), nucleotide supplements enhanced growth and maturation of both ce ll lines. We conclude that the de novo biosynthesis of nucleotides is sufficient to support proliferation of tumor Caco-2 cells but not of t he normal crypt IEC-6 cells. Thus, nucleotide supplements may enhance normal enterocyte growth and maturation as well as spare the need for exogenous glutamine in cell maintenance and development.