Nicotinamide deficiency in human lymphocytes prevents the [3H]thymidine-induced adaptive response for the repair of X-ray-induced chromosomal damage.
Human lymphocytes treated with [3H]thymidine ([3H]dThd) become refractory to the induction of chromosomal aberrations by subsequent doses of X rays. This adaptive response to [3H]dThd does not occur in the presence of 3-aminobenzamide (3AB). 3AB inhibits the synthesis of poly(ADP-ribose) by the enzyme adenosine diphosphate ribosyl transferase (ADPRT), which requires NAD as a substrate. 3AB also prevents chromosomal repair, as measured in X-ray dose-fractionation studies. Because 3AB might interfere with metabolic reactions other than those mediated by ADPRT, experiments were carried out to see if the adaptive response was also inhibited in nicotinamide-free medium, which prevents poly(ADP-ribosyl)ation by depleting cellular NAD. The experiments show that the incorporation of [3H]dThd has no effect on the induction of chromosomal aberrations by subsequent doses of X rays if the cells are cultured in nicotinamide-free medium. Nicotinamide deficiency mimics the effects of 3AB on both the adaptive response and chromosome repair. The results indicate that ADPRT activity itself, and not other metabolic processes affected by inhibitors of this enzyme, plays an essential role in the adaptive response.
D001549:Benzamides / Q000494:pharmacology; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects*; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology / Q000502:physiology*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013936:Thymidine / Q000494:pharmacology*
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D013936:Thymidine