Combination effects of poly(ADP-ribose) polymerase inhibitors and DNA-damaging agents in ovarian tumor cell lines - With special reference to cisplatin
Combination effects of poly(ADP-ribose) polymerase inhibitors and DNA-damaging agents in ovarian tumor cell lines - With special reference to cisplatin
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DOI：
10.1007/bf01209029
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发表时间：
1996-11-01
影响因子：
3.6
通讯作者：
Zeller, WJ
中科院分区：
文献类型：
--
作者：
Bernges, F;Zeller, WJ
研究了聚腺苷二磷酸核糖聚合酶抑制剂4-氨基-1，8-萘亚胺(4-ANI)、6(5H)-菲咯烷酮(PHD)、1，5-异喹啉(IQD)、3-氨基苯甲酰胺(3-AB)和4-羟基喹唑啉(4-HYA)对顺铂细胞毒性的影响。采用人卵巢癌细胞株SK-OV-3、OAW42和大鼠卵巢癌细胞株O-342及其顺铂耐药亚系O-342/DDP。用四甲基偶氮唑蓝(3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)比色法测定细胞毒作用。以1-甲基-3-硝基-1-亚硝基-1-亚硝基(MNNG)及其与聚腺苷二磷酸核糖聚合酶抑制剂的联合应用为阳性对照。此外，烷基化试剂L-苏糖醇-1，4-二甲基磺酸盐(DHB)和1，3-二(2-氯乙基)-1-亚硝脲(卡莫司汀)以及另外两种DNA修复抑制剂咖啡因和茶碱也被纳入研究范围。4-ANI、PHD、IQD、4-HYA、3-AB不能增强顺铂的细胞毒作用，咖啡因可增强O-342/DDP和SK-OV-3细胞的细胞毒作用，茶碱可增强O-342/DDP、SK-OV-3和OAW42细胞的细胞毒作用。除OAW42外，MNNG与4-ANI、PHD、IQD、4-HYA、3-AB或茶碱联合使用均可增强MNNG的细胞毒作用，后者仅有4-ANI、PHD和IQD增强MNNG的细胞毒作用。4-ANI、PHD、4-HYA、茶碱和咖啡因对O-342/DDP细胞的细胞毒作用增强，SK-OV-3细胞被4-HYA、茶碱和咖啡因增强，OAW42细胞对茶碱和咖啡因的细胞毒作用增强。卡莫司汀对SK-OV-3和OAW42细胞株的细胞毒作用仅被3-AB增强。对不同的DNA修复机制的结果进行了讨论。
The effects of the poly(ADP-ribose) polymerase inhibitors 4-amino-1,8-naphthalimide (4-ANI), 6(5H)-phenanthridinone (PHD), 1,5-isoquinolinediol (IQD), 3-aminobenzamide (3-AB) or 4-hydroxyquinazoline (4-HYA) on the cytotoxicity of cisplatin were investigated. The human ovarian tumor cell lines SK-OV-3 and OAW 42 and the rat ovarian tumor cell line O-342 as well as its cisplatin(DDP)-resistant subline O-342/DDP were used. Cytotoxicity was determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) plus its respective combinations with poly(ADP-ribose) polymerase inhibitors served as positive controls. In addition, the alkylating agents L-threitol-1,4-bismethanesulfonate (DHB) and 1,3-bis (2-chloroethyl)-1-nitrosourea (carmustine) as well as two other DNA-repair inhibitors caffeine and theophylline were included in the investigations. The cytotoxicity of cisplatin could not be increased by 4-ANI, PHD, IQD, 4-HYA or 3-AB in any cell line investigated, while it was increased by caffeine in lines O-342/DDP and SK-OV-3 as well as by theophylline in lines O-342/DDP, SK-OV-3 and OAW 42. The cytotoxicity of MNNG was increased by combination with 4-ANI, PHD, IQD, 4-HYA, 3-AB or theophylline for all lines except OAW42; in the latter line, only 4-ANI, PHD and IQD increased MNNG cytotoxicity. The cytotoxicity of DHB was increased by 4-ANI, PHD, 4-HYA, theophylline and caffeine in line O-342/DDP; by 4-HYA, theophylline and caffeine in line SK-OV-3; and by theophylline and caffeine in line OAW42. The cytotoxicity of carmustine was increased only by 3-AB in two lines (SK-OV-3 and OAW 42). Results are discussed with regard to different DNA-repair mechanisms.