Large supplements of nicotinic acid and nicotinamide increase tissue NAD+ and poly(ADP-ribose) levels but do not affect diethylnitrosamine-induced altered hepatic foci in Fischer-344 rats.
Poly(ADP-ribose) is a homopolymer of ADP-ribose units synthesized from NAD+ on nuclear acceptor proteins and is known to be involved in DNA repair. It is not known whether large oral doses of the clinically utilized NAD precursors nicotinic acid or nicotinamide affect poly(ADP-ribose) metabolism or the cellular response to DNA damage. In our first study, using Fischer-344 rats, 2 wk of dietary nicotinic acid supplementation (500 and 1000 mg/kg diet) caused elevated levels of NAD+ in the blood, liver, heart and kidney, while nicotinamide caused elevated levels only in the blood and liver, compared with controls fed a diet containing 30 mg/kg nicotinic acid. Both nicotinic acid and nicotinamide, at 1000 mg/kg diet, caused elevations in liver NAD+, by 44 and 43%, respectively. Only nicotinamide, however, elevated liver poly(ADP-ribose) (63% higher than control group). Following treatment with the hepatocarcinogen diethylnitrosamine, higher levels of hepatic NAD+ were observed in rats fed both nicotinic acid and nicotinamide at 1000 mg/kg diet, but only nicotinic acid supplementation caused a greater accumulation of hepatic poly(ADP-ribose) (61% higher than control group). Neither of the dietary treatments significantly affected the proportion of the liver occupied by placental glutathione-S-transferase positive foci. These results show that poly(ADP-ribose) synthesis is not directly responsive to hepatic NAD+ levels during niacin supplementation, and that the mechanisms of action of nicotinic acid and nicotinamide are different. The observed changes in poly(ADP-ribose) metabolism do not appear to cause any change in susceptibility to chemically induced carcinogenesis in this organ.
Jackson
T M
TM
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
Rawling
J M
JM
Roebuck
B D
BD
Kirkland
J B
JB
D000246:Adenosine Diphosphate Ribose / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D004052:Diethylnitrosamine / Q000494:pharmacology*; D005527:Food, Fortified; D005982:Glutathione Transferase / Q000032:analysis; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009243:NAD / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D009525:Niacin; D004052:Diethylnitrosamine; D005982:Glutathione Transferase