Exogenous nucleosides modulate proliferation of rat intestinal epithelial IEC-6 cells

Exogenous nucleotides are considered serniessential nutritional components that play an important role in intestinal development, maintenance, and recovery from tissue damage. Nucleosides (NS) are the best-absorbed chemical form of nucleotides in the intestinal epithelium. The aim of this work was to clarify, at the cellular level, the effects described in vivo. Under conditions of high intracellular availability of NS, we studied the effects of 2 NS mixtures on the NS uptake and intracellular distribution and on the proliferation, morphology, viability, and cell-cycle phase distribution of rat intestinal epithelial cell line 6. Purine and pyrimidine NS showed a similar uptake profile, but the intracellular incorporation of guanosine was greater than that of undine, without differences in intracellular distribution. Proliferation assays demonstrated that IEC-6 cell proliferation is increased by a mixture containing thymidine but decreased by one containing uridine. In fact, the antiproliferative effect started at 75 mu mol/L, which indicated that it may not be correct to consider concentrations of uridine > 75 mu mol/L as physiological. Interestingly, these effects were not related to increased cell necrosis or apoptosis or to changed cell morphology but rather to a reduced S-phase and increased GO/G1 phase of the cell cycle. In summary, our results suggest that NS molecules are well-absorbed by rat intestinal epithelial cell line 6 cells, whose proliferation can be promoted or inhibited (according to the NS mixtures used) by a mechanism that is not dependent on the toxicity of the mixtures.