THE EFFECT OF NIACIN DEFICIENCY ON DIETHYLNITROSAMINE-INDUCED HEPATICPOLY(ADP-RIBOSE) LEVELS AND ALTERED HEPATIC FOCI IN THE FISCHER-344 RAT

Poly(ADP-ribose) is synthesized on nuclear proteins in response to DNA damage and plays an important role in DNA repair. Niacin and tryptoph an are dietary precursors to NAD(+), which is the substrate for poly(A DP-ribose) synthesis. This study examined the influence of niacin stat us on poly(ADP-ribose) metabolism and carcinogenesis. Diets devoid of added niacin, with different levels of tryptophan, were used to produc e moderate and severe niacin deficiencies in male Fischer-344 rats. Co ntrol 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. Wh ereas blood and liver NAD(+) were decreased by niacin deficiency, bloo d NAD(+) was not affected by DEN. Liver NAD(+) decreased significantly in response to DEN treatment in the pair-fed groups, but it did not c hange in the niacin-deficient groups. Unexpectedly, at 10 hours postin jection, 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-de ficient livers. In Experiment 2, livers were examined for the presence of alter ed hepatic foci three months after DEN exposure. There were no significant differences in the percentage of liver occupied by foci between the niacin-deficient and pair-fed groups (n = 8). These resul ts indicate that niacin-deficient rats were able to accumulate higher concentrations of hepatic poly(ADP-ribose) in response to DEN and did not show elevated susceptibility to initiation of altered hepatic foci .