Dietary nucleotides and intestinal cell lines: I. Modulation of growth

Emerging evidence suggests that nucleotide-free diets induce immune suppression and may seriously influence intestinal growth, maturation, and function. Thus, DNA-Na+ salt from fish soft roe, used as a nucleotide source, was investigated in regard to its effect on intestinal growth under optimal and nutrition-depleted conditions. The effect of another dietary additive, RNA from bakers yeast (S. cerevisiae) and various deoxy-mononucleotides have also been clarified. DNA-Na+, RNA, dAMP, dCMP, dGMP, and TMP were added to a human malignant intestinal cell line, CaCo-2 and a rat intestinal cell line of normal origin, IEC-6. Growth effects were ascertained by measuring the amount of tritium-labeled thyrnidine incorporated into the cell DNA. Our results show that DNA-Na+, RNA, and deoxy-mononucleotides have beneficial effects on growth, trying to compensate for the glutamine- and partially serum-deprived culture condition, depending on the intestinal cell line investigated. Especially the normal IEC-6 cell fine seemed to benefit from the exogenous nucleotide supply. dAMP increased mostly CaCo-2 growth under optimal conditions. Both dCMP and dGMP supported growth of both cell lines under most culture conditions. In contrast, TMP acted as a general growth inhibitor. Of interest also was the growth-suppressing ability of DNA-Na+ in particular, but also RNA, on vigorously proliferating CaCo-2 cells cultured under optimal nutrition supply. This activity should be investigated in regard to other hyperproliferating and malignant cell types. (C) 2004 Elsevier Inc. All rights reserved.