Preventive Effect of 3‐Aminobenzamide on the Reduction of NAD Levels in Rat Liver Following Administration of Diethylnitrosamine

Abstract

Nicotinamide adenine dinucleotide is utilized as the substrate of a chromatin‐bound enzyme, poly(ADP‐ribose) polymerase. The effects of diethylnitrosamine and/or 3‐aminobenzamide, a potent inhibitor of poly(ADP‐ribose) polymerase, on the cellular NAD levels in rat liver were investigated. 3‐Aminobenzamide (600 mg/kg) administered intraperitoneally was not detectable in the liver within 12 hr after administration; the inhibitor had a calculated half life of 90 min. Diethylnitrosamine reduced the NAD levels in rat liver in a dose‐dependent way. The NAD content reached a minimum level at 8 hr, returning to 78% of the control value after 48 hr. The reduction of the NAD levels caused by diethylnitrosamine was completely prevented when 3‐aminobenzamide was administered either simultaneously with diethylnitrosamine or 4 hr after diethylnitrosamine treatment. Furthermore, an immunohistochemical study showed that nuclear poly(ADP‐ribose) decreased 1 hr after the administration of 3‐aminobenzamide. These results suggest that inhibition of poly(ADF‐ribosyl)ation is involved in the initiation of liver carcinogenesis by diethylnitrosamine and 3‐aminobenzamide. Copyright © 1988, Wiley Blackwell. All rights reserved