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
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.