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Title: Involvement of NAD metabolism in the cellular response to DNA damage
Author: Halldorsson, H.
ISNI:       0000 0001 3527 6910
Awarding Body: University of Sussex
Current Institution: University of Sussex
Date of Award: 1978
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In this thesis I show that treatment of mouse lymphoma cells with~adiation or the alkylating agent streptozotocin increases the activity of the chromosomal enzyme poly(ADP-ribose)polymerase. This activation is observed using a new assay for poly(ADP-ribose)polymerase using cells rendered permeable to nucleotides by treatment with hypotonic buffer. Employing this assay the activity of poly(ADP-ribose) polymerase is much lower than that of isolated nuclei. Evidence is presented to show that the high activity of isolated nuclei is an artifact of the isolation procedure and that this is caused by the fragmentation of DNA during the nuclear isolation. Streptozotocin causes a transient loss of NAD nucleotides. I show that this can be prevented by concomittant administration of inhibitors of poly(ADP-ribose)polymerase and that this treatment increases the cytotoxicity of streptozotocin. Similar effects on NAD levels and their prevention by poly(ADP-ribose)polymerase inhibitors have been observed with ionizing irradiation and several alkylating agents. I suggest that the activation of poly(ADP-ribose)polymerase is the reason for the NAD loss and that this activation is caused by the DNA damage caused by these agents. The effects of cytotoxic agents on NAD metabolism are reviewed and the results are discussed in : relation to the possible interactions of DNA and energy metabolism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available