title: Exogenous nucleosides modulate proliferation of rat intestinal epithelial IEC-6 cells.
abstract: Exogenous nucleotides are considered semiessential 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 uridine, 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 micromol/L, which indicated that it may not be correct to consider concentrations of uridine >75 micromol/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 G0/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.
authors: Department of Health Science, University of Jaén, 23071 Jaén, Spain.
authors: Fernando
authors: F
authors: Rodríguez-Serrano
authors: Juan A
authors: JA
authors: Marchal
authors: Antonio
authors: A
authors: Ríos
authors: Antonio
authors: A
authors: Martínez-Amat
authors: Houria
authors: H
authors: Boulaiz
authors: José
authors: J
authors: Prados
authors: Macarena
authors: M
authors: Perán
authors: Octavio
authors: O
authors: Caba
authors: Esmeralda
authors: E
authors: Carrillo
authors: Fidel
authors: F
authors: Hita
authors: Antonia
authors: A
authors: Aránega
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001345:Autoradiography; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000378:metabolism; D004338:Drug Combinations; D007413:Intestinal Mucosa / Q000166:cytology* / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D009705:Nucleosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014018:Tissue Distribution
chemical_list: D003470:Culture Media; D004338:Drug Combinations; D009705:Nucleosides