Abstract
Several reports indicate that intracellular levels of NAD are rapidly decreased by DNA-damaging agents such as strep-tozotocin1–7, neocarzinostatin8,9 and ionising radiation8–11. Similarly, evidence obtained from studies in isolated nuclei and permeabilised cells indicates that DNA damage caused by several alkylating chemicals12–15, X rays16,17 and DNA-hydrolysing enzymes18,19 elicit a considerable increase in the activity of poly(ADP-ribose) polymerase, a chromosomal enzyme which uses NAD as a substrate in the formation of poly(ADP-ribose) in histones and other nuclear proteins20,21. Thus, it has been suggested that DNA-damaging agents lower NAD levels by causing an increase in poly(ADP-ribose) synthesis9,12,13. As DNA damage initiates DNA repair mechanisms, it has also been argued that poly(ADP-ribose) is involved in DNA repair8,12,14,17,22,23. Such possibilities would be strongly supported if an actual increase in the intracellular levels of poly(ADP-ribose) could be shown to occur after induction of DNA damage. We now present data obtained using a new technique which has enabled us to measure the levels of poly(ADP-ribose) in vivo in SV40 virus-transformed 3T3 cells (SVT2). We show that treatment of these cells with the powerful mutagen N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) produces, concomitantly with a decrease in NAD levels, a dramatic increase in the intracellular levels of poly (ADP-ribose).
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Juarez-Salinas, H., Sims, J. & Jacobson, M. Poly(ADP-ribose) levels in carcinogen-treated cells. Nature 282, 740–741 (1979). https://doi.org/10.1038/282740a0
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DOI: https://doi.org/10.1038/282740a0
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