Bernges F, Zeller W J
German Cancer Research Center, Heidelberg, Germany.
J Cancer Res Clin Oncol. 1996;122(11):665-70. doi: 10.1007/BF01209029.
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.
研究了聚（ADP - 核糖）聚合酶抑制剂4 - 氨基 - 1,8 - 萘二甲酰亚胺（4 - ANI）、6（5H） - 菲啶酮（PHD）、1,5 - 异喹啉二醇（IQD）、3 - 氨基苯甲酰胺（3 - AB）或4 - 羟基喹唑啉（4 - HYA）对顺铂细胞毒性的影响。使用了人卵巢肿瘤细胞系SK - OV - 3和OAW 42、大鼠卵巢肿瘤细胞系O - 342及其顺铂（DDP）耐药亚系O - 342/DDP。用3 - （4,5 - 二甲基噻唑 - 2 - 基） - 2,5 - 二苯基四氮唑溴盐（MTT）法测定细胞毒性。1 - 甲基 - 3 - 硝基 - 1 - 亚硝基胍（MNNG）及其与聚（ADP - 核糖）聚合酶抑制剂的各自组合作为阳性对照。此外，研究中还包括烷基化剂L - 苏糖醇 - 1,4 - 双甲磺酸酯（DHB）和1,3 - 双（2 - 氯乙基） - 1 - 亚硝基脲（卡莫司汀）以及另外两种DNA修复抑制剂咖啡因和茶碱。在所研究的任何细胞系中，4 - ANI、PHD、IQD、4 - HYA或3 - AB均不能增加顺铂的细胞毒性，而咖啡因在O - 342/DDP和SK - OV - 3细胞系中可增加其细胞毒性，茶碱在O - 342/DDP、SK - OV - 3和OAW 42细胞系中可增加其细胞毒性。除OAW42细胞系外，MNNG与4 - ANI、PHD、IQD、4 - HYA、3 - AB或茶碱联合使用可增加其细胞毒性；在后者细胞系中，只有4 - ANI、PHD和IQD可增加MNNG的细胞毒性。在O - 342/DDP细胞系中，4 - ANI、PHD、4 - HYA、茶碱和咖啡因可增加DHB的细胞毒性；在SK - OV - 3细胞系中，4 - HYA、茶碱和咖啡因可增加其细胞毒性；在OAW42细胞系中，茶碱和咖啡因可增加其细胞毒性。卡莫司汀的细胞毒性仅在SK - OV - 3和OAW 42两个细胞系中被3 - AB增加。针对不同的DNA修复机制对结果进行了讨论。
