Abstract
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.
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Abbreviations
- LY-R:
-
L5178Y-R murine lymphoma cell
- LY-S cells:
-
L5178Y-S murine lymphoma cell
- UV254nm :
-
ultraviolet light of 254 nm
- ∈-RAdo, 1:
-
N6-ethenoribosyladenosine
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Kleczkowska, H.E., Szumiel, I. & Althaus, F.R. Adaptive changes in NAD+ metabolism in ultraviolet light-irradiated murine lymphoma cells. Cell Biol Toxicol 6, 259–268 (1990). https://doi.org/10.1007/BF02443801
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DOI: https://doi.org/10.1007/BF02443801