Uchida K, Takahashi S, Fujiwara K, Ueda K, Nakae D, Emi Y, Tsutsumi M, Shiraiwa K, Ohnishi T, Konishi Y
Department of Oncological Pathology, Nara Medical College.
Jpn J Cancer Res. 1988 Oct;79(10):1094-100. doi: 10.1111/j.1349-7006.1988.tb01532.x.
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(ADP-ribosyl)ation is involved in the initiation of liver carcinogenesis by diethylnitrosamine and 3-aminobenzamide.
烟酰胺腺嘌呤二核苷酸被用作一种与染色质结合的酶——聚（ADP - 核糖）聚合酶的底物。研究了二乙基亚硝胺和/或聚（ADP - 核糖）聚合酶的强效抑制剂3 - 氨基苯甲酰胺对大鼠肝脏细胞内烟酰胺腺嘌呤二核苷酸（NAD）水平的影响。腹腔注射的3 - 氨基苯甲酰胺（600毫克/千克）在给药后12小时内肝脏中无法检测到；该抑制剂的计算半衰期为90分钟。二乙基亚硝胺以剂量依赖的方式降低大鼠肝脏中的NAD水平。NAD含量在8小时时达到最低水平，48小时后恢复到对照值的78%。当3 - 氨基苯甲酰胺与二乙基亚硝胺同时给药或在二乙基亚硝胺处理后4小时给药时，二乙基亚硝胺引起的NAD水平降低被完全阻止。此外，免疫组织化学研究表明，在给予3 - 氨基苯甲酰胺1小时后，细胞核中的聚（ADP - 核糖）减少。这些结果表明，聚（ADP - 核糖）化的抑制参与了二乙基亚硝胺和3 - 氨基苯甲酰胺引发的肝脏致癌作用。
