Aluminum inhibition of ADP-ribosylation in vivo and in vitro.

Aluminum accumulates on DNA containing nuclear structures in several human degenerative brain diseases and following the direct injection of aluminum into the brain of certain experimental animals. The enzyme poly(ADP-ribose) synthetase is activated following DNA damage. Aluminum added to nuclei, in vitro, at concentrations approaching that necessary to induce a progressive encephalopathy in animals, reduces poly(ADP-ribose) formation to 75% of control. Nuclei extracted at various stages of the aluminum encephalopathy exhibit a reduction in ADP-ribosylation to 50% of control nuclei. Altered ADP-ribosylation may be an important nuclear consequence of aluminum toxicity in both the experimental models and in degenerative human brain disease.