POLY(ADP-RIBOSE) POLYMERASE-ACTIVITY AND DNA STRAND BREAKS ARE AFFECTED IN TISSUES OF NIACIN-DEFICIENT RATS

Citation
Jz. Zhang et al., POLY(ADP-RIBOSE) POLYMERASE-ACTIVITY AND DNA STRAND BREAKS ARE AFFECTED IN TISSUES OF NIACIN-DEFICIENT RATS, The Journal of nutrition, 123(8), 1993, pp. 1349-1355
Citations number
27
Categorie Soggetti
Nutrition & Dietetics
Journal title
ISSN journal
00223166
Volume
123
Issue
8
Year of publication
1993
Pages
1349 - 1355
Database
ISI
SICI code
0022-3166(1993)123:8<1349:PPADSB>2.0.ZU;2-V
Abstract
The niacin cofactor, NAD, is the substrate for poly(ADP-ribose) polyme rase, 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-def icient 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 mai ntained rats in a deficient state for 1 mo, and, when the dietary niac in 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 expo sed 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 hep atic poly(ADP-ribose) polymerase activity can be elevated, a severe ni acin deficiency may increase the susceptibility of DNA to oxidative da mage, likely due to a lower availability of NAD.