Adaptive changes in NAD+ metabolism in ultraviolet light-irradiated murine lymphoma cells.
We have determined the ability of UV254nm-irradiated murine lymphoma cells to adapt their NAD+ metabolism to the increased NAD+ consumption for the poly ADP-ribosylation of chromatin proteins. Two murine lymphoma sublines with differential UV-sensitivity and poly(ADP-ribose) turnover were used as a model system. The first subline, designated LY-R is UV254nm-sensitive and tumorigenic in DBA/2 mice. The second subline, LY-S is UV254nm-resistant and nontumorigenic. Following treatment of these cells with 2 mM benzamide, an inhibitor of the NAD(+)-utilizing enzyme poly(ADP-ribose) polymerase, NAD+ levels slowly increased up to about 160% of control levels after 3 hours. When benzamide was added to these cultures 20 min after UV254nm irradiation, a dramatic transient increase of NAD+ levels was observed within 4 min in LY-R cells and more moderately in LY-S cells. At later times after UV254nm irradiation, the NAD+ levels increased in both sublines reaching up to 200% of the concentrations prior to benzamide treatment. These results demonstrate an adaptative response of NAD+ metabolism to UV254nm irradiation. In parallel, we observed a differential repartitioning of ADP-ribosyl residues between the NAD+ and poly(ADP-ribose) pools of LY-R and LY-S cells that correlates with the differential UV sensitivity of these cells.
Kleczkowska
H E
HE
Institute of Nuclear Chemistry and Technology, Warsaw, Poland.
Szumiel
I
I
Althaus
F R
FR
D000222:Adaptation, Physiological; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001549:Benzamides; D002452:Cell Count / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D008223:Lymphoma; D051379:Mice; D009243:NAD / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D000246:Adenosine Diphosphate Ribose; C037689:benzamide