DIETARY NIACIN DEFICIENCY LOWERS TISSUE POLY(ADP-RIBOSE) AND NAD(+) CONCENTRATIONS IN FISCHER-344 RATS

Poly(ADP-ribose) is synthesized in response to DNA strand breaks, using NAD(+) as substrate, and has been implicated in the process of DNA repair. Because NAD(+) can be synthesized from niacin or tryptophan, both of these components must be manipulated to alter niacin status. Six dietary treatments were used, including niacin-deficient (ND) diets and niacin-replete (NR) diets consumed ad libitum and the NR diets pair-fed (PF) to the ND intake. The ND, NR and PF diets contained either 80 g casein + 50 g gelatin/kg diet (8-5 diets) or 70 g casein + 60 g gelatin/kg diet (7-6 diets) to control tryptophan content. The 8-5ND and 7-6ND diets induced mild and severe symptoms of niacin-deficiency, respectively, over a 3-wk period in male weanling Fischer-344 rats. Food intake and weight gain were suppressed in both of the ND groups compared with their- respective INR controls. Weight gain was not different between ND animals and their PF counterparts. At 3 wk, blood, liver, kidney, heart and lung NAD(+) concentrations for both 8-5ND and 7-6ND animals were all significantly lower than those for their respective PF groups. In the groups fed the 8-5 diets, liver poly(ADP-ribose) was lower in the ND group (64% of PF), with no difference between the NR and PF groups. In rats fed the 7-6 diets, poly(ADP-ribose) levels were further decreased in the ND group (43% of PF), but food restriction also exerted an independent effect (PF levels were 46% of NR levels). These data show that even a mild niacin deficiency decreases liver poly(ADP-ribose) concentrations and that poly(ADP-ribose) levels are altered by food restriction in niacin-replete animals.