Konishi Y, Takahashi S, Ohnishi T, Denda A, Mikami S, Emi Y, Nakae D
Princess Takamatsu Symp. 1983;13:309-19.
In the present experiments, we studied the effect of poly(ADP-ribose) polymerase inhibitors on the early stage of liver carcinogenesis by diethylnitrosamine (DEN) in rat liver in order to clarify the biological role of this enzyme in cancer induction. We used 3-aminobenzamide(ABA), 5-methylnicotinamide(MNam), and thymidine as the inhibitors and measured the numbers and sizes of gamma-glutamyltranspeptidase (gamma-GTP) positive foci as a marker of initiated cell populations. When ABA was given within 4 hr after DEN treatment, it had almost the same effect as a partial hepatectomy and caused dose-dependent enhancement of the induction of gamma-GTP positive foci. The administration of ABA at a dose of 600 mg/kg was effective to enhance the induction of the foci 1 day before to 1 day after 20 mg/kg DEN initiation. The enhancing effect of MNam and thymidine at a dose of 600 mg/kg was observed to the same extent as that of ABA. Based on these results the experiments were extended to the mechanisms of the enhancing effect of ABA. Liver cell necrosis was not detected by measuring serum GOT and GPT levels and histology after DEN and ABA administration. Further, the initiating and promoting activities of ABA in liver carcinogenesis were studied and ABA per se was not found to take part in either activity. These results indicate that poly(ADP-ribose) polymerase plays an important role in the early stage of liver carcinogenesis by DEN and provides a new avenue for studying the mechanisms of the initiation process in chemical carcinogenesis.
在本实验中，我们研究了聚（ADP - 核糖）聚合酶抑制剂对大鼠肝脏中二乙基亚硝胺（DEN）诱导肝癌早期阶段的影响，以阐明该酶在癌症诱发中的生物学作用。我们使用3 - 氨基苯甲酰胺（ABA）、5 - 甲基烟酰胺（MNam）和胸腺嘧啶作为抑制剂，并测量γ - 谷氨酰转肽酶（γ - GTP）阳性灶的数量和大小，将其作为起始细胞群体的标志物。当在DEN处理后4小时内给予ABA时，其效果几乎与部分肝切除相同，并导致γ - GTP阳性灶诱导的剂量依赖性增强。在20mg/kg DEN启动前1天至启动后1天，给予600mg/kg剂量的ABA可有效增强灶的诱导。观察到600mg/kg剂量的MNam和胸腺嘧啶的增强作用与ABA相同。基于这些结果，实验扩展到ABA增强作用的机制。在给予DEN和ABA后，通过测量血清谷草转氨酶（GOT）和谷丙转氨酶（GPT）水平以及组织学检查未检测到肝细胞坏死。此外，研究了ABA在肝癌发生中的启动和促进活性，未发现ABA本身参与任何一种活性。这些结果表明，聚（ADP - 核糖）聚合酶在DEN诱导的肝癌早期阶段起重要作用，并为研究化学致癌作用中起始过程的机制提供了新途径。
