The effect of niacin deficiency on diethylnitrosamine-induced hepatic poly(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 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-deficient livers. In Experiment 2, livers were examined for the presence of altered 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 results 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.
Rawling
J M
JM
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
Jackson
T M
TM
Roebuck
B D
BD
Poirier
G G
GG
Kirkland
J B
JB
D000818:Animals; D004052:Diethylnitrosamine / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009243:NAD / Q000378:metabolism*; D009525:Niacin / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014364:Tryptophan / Q000494:pharmacology
D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D009525:Niacin; D004052:Diethylnitrosamine; D014364:Tryptophan; D005982:Glutathione Transferase