title: Modulatory effect of nicotinamide on unscheduled DNA synthesis in lymphocytes from young and old mice.
abstract: We studied the DNA repair capacity, as measured by unscheduled DNA synthesis, of resting lymphocytes from a long-lived strain of mouse after UV irradiation. Lymphocytes from old mice showed a lower level of repair than lymphocytes from young mice. After in vitro treatment with nicotinamide, a precursor of cellular NAD+, the level of UV-induced DNA repair increased in resting lymphocytes from both young and old mice. This effect was more dramatic in old mice, which showed a twofold relative increase in repair. Nicotinamide at a concentration of 0.5-5 mM did not inhibit the proliferation of concanavalin A (Con A) stimulated mouse lymphocytes; on the contrary, 3-amino benzamide, a potent poly(ADP-ribose)polymerase inhibitor, strongly affected the lymphocyte responsiveness to Con A. Nicotinamide did not significantly increase the UV-induced DNA repair in lymphocytes stimulated to proliferate by Con A. However, Con A activated, but non-proliferating (hydroxyurea-treated) lymphocytes from old mice displayed a level of DNA repair similar to that of lymphocytes from young animals. These results suggest that one of the limiting factors affecting the DNA repair activity of resting lymphocytes from old mice is the level of intracellular NAD+.
mesh_terms: D000375:Aging; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects* / Q000528:radiation effects; D006918:Hydroxyurea / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D009536:Niacinamide / Q000494:pharmacology*
chemical_list: D003208:Concanavalin A; D009536:Niacinamide; D006918:Hydroxyurea