Poly(ADP-ribose) polymerase activity and DNA strand breaks are affected in tissues of niacin-deficient rats.
The niacin cofactor, NAD, is the substrate for poly(ADP-ribose) polymerase, an enzyme associated with DNA repair. We investigated, therefore, whether hepatic poly(ADP-ribose) polymerase activity was altered and DNA strand breaks in lymphocytes and liver were greater in niacin-deficient rats. A niacin deficiency was established in weanling rats with diets containing 1.5 mg/kg of niacin. Based on lower growth rates and NAD concentrations in blood, liver and skeletal muscle, this diet maintained rats in a deficient state for 1 mo, and, when the dietary niacin was reduced to 0.5 mg/kg, rats remained deficient for an additional month. The hepatic poly(ADP-ribose) polymerase activity was decreased in one experiment when mean hepatic NAD concentrations were 0.60 and 0.51 mumol/g at d 34 and d 60, respectively, compared with 0.77 and 0.80 mumol/g in pair-fed controls. Enzyme activity, however, was greater than in controls when hepatic NAD concentrations were < 0.30 mumol/g. Strand breaks in DNA did not accumulate except after tissues were exposed to hypoxanthine-xanthine oxidase, a free radical-generating system. Exposure to this system caused more DNA strand breaks in lymphocytes and hepatic nuclei from niacin-deficient rats compared with the same tissues from controls. The results suggest that, in rats, although hepatic poly(ADP-ribose) polymerase activity can be elevated, a severe niacin deficiency may increase the susceptibility of DNA to oxidative damage, likely due to a lower availability of NAD.
Zhang
J Z
JZ
School of Public Health, University of California, Los Angeles 90024.
Henning
S M
SM
Swendseid
M E
ME
D000818:Animals; D001835:Body Weight; D004249:DNA Damage; D004435:Eating; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology; D008297:Male; D009132:Muscles / Q000737:chemistry / Q000473:pathology; D009243:NAD / Q000032:analysis / Q000097:blood; D009525:Niacin / Q000172:deficiency*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000737:chemistry / Q000473:pathology; D014364:Tryptophan / Q000008:administration & dosage; D014804:Vitamin B Deficiency / Q000201:enzymology / Q000473:pathology; D015430:Weight Gain
D009243:NAD; D009525:Niacin; D014364:Tryptophan; D011065:Poly(ADP-ribose) Polymerases