The effect of niacin deficiency on diethylnitrosamine-induced hepatic poly(ADP-ribose) levels and altered hepatic foci in the Fischer-344 rat

Nutrition and Cancer
J M RawlingJames B Kirkland

Abstract

Poly(ADP-ribose) is synthesized on nuclear proteins in response to DNA damage and plays an important role in DNA repair. Niacin and tryptophan are dietary precursors to NAD+, which is the substrate for poly(ADP-ribose) synthesis. This study examined the influence of niacin status on poly(ADP-ribose) metabolism and carcinogenesis. Diets devoid of added niacin, with different levels of tryptophan, were used to produce moderate and severe niacin deficiencies in male Fischer-344 rats. Control rats were pair fed niacin-replete diets. After a 21-day feeding period, rats were injected with diethylnitrosamine (DEN) (Expt 1, 200 mg/kg ip; Expt 2, 100 mg/kg ip). In Experiment 1, blood and liver NAD+ and liver poly(ADP-ribose) were measured over the next 15 hours. Whereas blood and liver NAD+ were decreased by niacin deficiency, blood NAD+ was not affected by DEN. Liver NAD+ decreased significantly in response to DEN treatment in the pair-fed groups, but it did not change in the niacin-deficient groups. Unexpectedly, at 10 hours postinjection, liver poly(ADP-ribose) accumulation was greater (p < 0.05) in the niacin-deficient than in the pair-fed rats (n = 9), despite lower initial NAD+ levels and a lack of NAD+ disappearance in niacin-def...Continue Reading

References

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Citations

Apr 11, 2001·Mutation Research·G J Hageman, R H Stierum
Dec 6, 2011·Mutation Research·James B Kirkland
Jan 30, 2013·Molecular Aspects of Medicine·Carles CantóPeter Bai
Dec 24, 2003·Nutrition and Cancer·James B Kirkland
May 14, 2010·Experimental Biology and Medicine·James B Kirkland
Apr 17, 2019·Molecular Nutrition & Food Research·Wenbiao ShiJaap Keijer
Apr 4, 2021·Metabolites·Maria Del Mar Romero-LopezJose L Peiro

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