Sekiya S, Oosaki T, Andoh S, Suzuki N, Akaboshi M, Takamizawa H
Department of Obstetrics and Gynceology, Chiba University School of Medicine, Japan.
Eur J Cancer Clin Oncol. 1989 Mar;25(3):429-37. doi: 10.1016/0277-5379(89)90255-1.
A cis-diamminedichloroplatinum (II) (cisplatin)-resistant subline (Cis-Ptr) demonstrated 20-fold greater resistance to the cytotoxic effects of cisplatin, compared with the parental cloned rat ovarian carcinoma cell line (ROT 68/C1). The uptake of cisplatin into the Cis-Ptr cells was identical to that into the ROT68/C1 cells in vitro and in vivo. Glutathione activity in a cytoplasmic extract was 1.4-fold and 1.8-fold greater in the Cis-Ptr cells than in the ROT68/C1 cells in vitro and in vivo, respectively. There was no difference between the ROT68/C1 and Cis-PTr cells in 195m cisplatin binding per micrograms DNA. DNA repair of cisplatin DNA damage was increased in the Cis-PTr cells but not in the ROT68/C1 cells. These results suggest that the mechanisms of resistance to cisplatin in rat ovarian carcinoma cells involve increased activity of the DNA repair system and increased cytosolic binding to thiols may also be involved.
与亲代克隆大鼠卵巢癌细胞系（ROT 68/C1）相比，顺式二氨二氯铂（II）（顺铂）耐药亚系（Cis-Ptr）对顺铂细胞毒性作用的耐药性高20倍。体外和体内实验中，顺铂进入Cis-Ptr细胞的摄取情况与进入ROT68/C1细胞的摄取情况相同。体外和体内实验中，细胞质提取物中的谷胱甘肽活性在Cis-Ptr细胞中分别比在ROT68/C1细胞中高1.4倍和1.8倍。每微克DNA的¹⁹⁵m顺铂结合量在ROT68/C1细胞和Cis-PTr细胞之间没有差异。顺铂DNA损伤的DNA修复在Cis-PTr细胞中增加，但在ROT68/C1细胞中未增加。这些结果表明，大鼠卵巢癌细胞对顺铂的耐药机制涉及DNA修复系统活性增加，并且可能还涉及胞质溶胶与硫醇结合增加。
