The effects of niacin deficiency and ethylnitrosourea treatment on NAD and poly(ADP-ribose) metabolism in rat bone marrow

dc.contributor.advisorKirkland, J.B.
dc.contributor.authorGallacher, Lisa M. of Human Biology and Nutritional Sciencesen_US of Guelphen_US of Scienceen_US
dc.description.abstractPrevious work has shown that niacin deficiency increases the severity of acute anemia and leukopenia in Long-Evans rats following chronic ethylnitrosourea (ENU) treatment. The research described in this thesis was designed to investigate the biochemical mechanisms responsible for this relative increase in bone marrow toxicity. Niacin, in the form of NAD$\sp{+},$ is required for the synthesis of poly(ADP-ribose) (pADPr) on nuclear proteins during DNA strand break rejoining. Inhibition of poly(ADP-ribosyl)ation has been shown to impair DNA repair, suggesting the importance of niacin status during the recovery from genotoxic stress. We hypothesize that niacin deficiency will decrease bone marrow NAD$\sp{+}$ levels, impairing pADPr synthesis and leading to the accumulation of DNA strand breaks following ENU treatment. These studies have shown that niacin deficiency decreases bone marrow NAD$\sp{+}$ levels in Long-Evans rats, yet in contrast to our hypothesis does not impair their ability to accumulate pADPr or rejoin DNA strand breaks following an acute challenge with ENU. Niacin deficient animals are able maintain poly(ADP-ribose) accumulation through enhanced NAD$\sp{+}$ biosynthesis, or undetermined changes in pADPr turnover.en_US
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectbiochemical mechanismen_US
dc.subjectbone marrow toxicityen_US
dc.subjectnuclear proteinsen_US
dc.subjectDNA repairen_US
dc.subjectniacin deficiencyen_US
dc.subjectDNA strand breaksen_US
dc.titleThe effects of niacin deficiency and ethylnitrosourea treatment on NAD and poly(ADP-ribose) metabolism in rat bone marrowen_US


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