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. 1988 Oct;79(10):1094–1100. doi: 10.1111/j.1349-7006.1988.tb01532.x

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

Kazuhiko Uchida 1,†, Seiichi Takahashi 1, Kunio Fujiwara 2, Kunihiro Ueda 3, Dai Nakae 1, Yohko Emi 1, Masahiro Tsutsumi 1, Kazumi Shiraiwa 1, Takeo Ohnishi 4, Yoichi Konishi 1,✉
PMCID: PMC5917636  PMID: 3143698

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.

Keywords: NAD levels, 3‐Aminobenzamide, Rat liver

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