Putrescine stimulates DNA synthesis in intestinal epithelial cells

Experiments were designed to examine the effects of exogenously supplied putrescine on the synthesis of DNA, RNA, and protein in cultured epithelial cells (IEC-6). Putrescine increased aphidicolin-sensitive DNA synthesis at concentrations as low as 0.3 μM putrescine with maximal stimulation (267% control) at 10 μM. This response appeared to be an effect of increases in the intracellular concentration of putrescine as the intracellular level of spermidine and spermine did not change over the time period examined. Furthermore, pulse-chase experiments revealed that putrescine that entered the cell was not metabolized to another polyamine or degraded. In addition, 10 μM putrescine enhanced both cycloheximide-sensitive lysine incorporation and actinomycin D-sensitive uridine incorporation, indexes of protein and RNA synthesis, respectively. Incorporation of both lysine and uridine was maximal 12 h after the addition of putrescine, whereas thymidine incorporation was still increasing at 24 h, the longest time point examined. These data suggest that putrescine synthesis and/or transport during mucosal proliferation is directly involved in the stimulation of epithelial DNA, RNA, and protein synthesis.