Tsujiuchi T, Tsutsumi M, Denda A, Kondoh S, Nakae D, Maruyama H, Konishi Y
Department of Oncological Pathology, Nara Medical College, Japan.
Carcinogenesis. 1990 Oct;11(10):1783-7. doi: 10.1093/carcin/11.10.1783.
The effects of inhibitors of poly(ADP-ribose)polymerase, 3-aminobenzamide (ABA), luminol and 3-methoxybenzamide (MBA) on the rat liver tumor promotion activity of phenobarbital (PB) were assessed. Fischer 344 male rats were initiated with N-nitrosodiethylamine (200 mg/kg) and placed on either basal diet, diet containing 0.05% PB, diet containing various doses of the inhibitors alone or diet containing 0.05% PB plus various doses of inhibitors for 10 weeks, and then killed. Quantitation of the development of glutathione S-transferase placental form-positive foci revealed that ABA at doses of 2 and 1.5, but not 1%, significantly inhibited the PB promotion activity. Luminol dose-dependently reduced PB promotion at doses of 3 and 6% but exerted no effects at the 1 and 2% levels. MBA also demonstrated a dose-dependent inhibitory influence at doses of 1 and 2%. The results are thus strongly suggestive of an involvement of poly ADP-ribosylation in the mechanisms underlying liver tumor promotion by PB.
评估了聚（ADP - 核糖）聚合酶抑制剂3 - 氨基苯甲酰胺（ABA）、鲁米诺和3 - 甲氧基苯甲酰胺（MBA）对苯巴比妥（PB）诱导大鼠肝肿瘤促进活性的影响。用N - 亚硝基二乙胺（200mg/kg）启动Fischer 344雄性大鼠，将其置于基础饮食、含0.05% PB的饮食、含不同剂量单一抑制剂的饮食或含0.05% PB加不同剂量抑制剂的饮食中10周，然后处死。对谷胱甘肽S - 转移酶胎盘型阳性灶的发育进行定量分析，结果显示，剂量为2%和1.5%而非1%的ABA显著抑制了PB的促进活性。鲁米诺在3%和6%的剂量下剂量依赖性地降低了PB的促进作用，但在1%和2%的水平上没有作用。MBA在1%和2%的剂量下也表现出剂量依赖性的抑制作用。因此，这些结果强烈提示多聚ADP - 核糖基化参与了PB促进肝肿瘤发生的机制。
