Chatterjee S, Cheng M F, Berger N A
Department of Medicine, University Hospitals of Cleveland, Ohio.
Cancer Commun. 1990;2(12):401-7. doi: 10.3727/095535490820873958.
Mutant V79 Chinese hamster cell lines, deficient in poly(ADP-ribose) polymerase activity, were previously shown to be significantly resistant to etoposide, a topoisomerase II inhibitor, and hypersensitive to camptothecin, a topoisomerase I inhibitor (Chatterjee, S.; Trivedi, D.; Petzold, S.J.; Berler, N.A. Mechanism of epipophyllotoxin-induced cell death in poly(adenosine diphosphate-ribose) synthesis-deficient V79 Chinese hamster cell lines. Cancer Res. 50:2713-2718, 1990 and Chatterjee, S.; Cheng, M.F.; Trivedi, D.; Petzold, S.J.; Berger, N.A. Camptothecin hypersensitivity in poly(adenosine diphosphate-ribose) polymerase-deficient cell lines. Cancer Commun. 1:389-394; 1990). We have now demonstrated hypersensitivity of these mutant cell lines, designated ADPRT 54 and ADPRT 351, to a variety of antitumor agents including melphalan, BCNU, mitomycin, and bleomycin. They are also hypersensitive to UV- and x-irradiation. These mutants, however, are significantly resistant to the topoisomerase II-targeted DNA intercalators, Adriamycin and m-AMSA. Our results strongly suggest that inhibition of poly(ADP-ribose) polymerase could be useful to potentiate the cytotoxicity of a variety of currently available antitumor drugs.
先前已表明，缺乏聚（ADP - 核糖）聚合酶活性的突变型V79中国仓鼠细胞系对拓扑异构酶II抑制剂依托泊苷具有显著抗性，而对拓扑异构酶I抑制剂喜树碱高度敏感（Chatterjee, S.; Trivedi, D.; Petzold, S.J.; Berler, N.A. 聚（腺苷二磷酸 - 核糖）合成缺陷型V79中国仓鼠细胞系中表鬼臼毒素诱导细胞死亡的机制。《癌症研究》50:2713 - 2718, 1990以及Chatterjee, S.; Cheng, M.F.; Trivedi, D.; Petzold, S.J.; Berger, N.A. 聚（腺苷二磷酸 - 核糖）聚合酶缺陷细胞系对喜树碱的超敏感性。《癌症通讯》1:389 - 394; 1990）。我们现已证明，这些命名为ADPRT 54和ADPRT 351的突变细胞系对多种抗肿瘤药物，包括美法仑、卡莫司汀、丝裂霉素和博来霉素高度敏感。它们对紫外线和X射线照射也高度敏感。然而，这些突变体对靶向拓扑异构酶II的DNA嵌入剂阿霉素和m - AMSA具有显著抗性。我们的结果强烈表明，抑制聚（ADP - 核糖）聚合酶可能有助于增强多种现有抗肿瘤药物的细胞毒性。
