Mechanisms of resistance to cis-diamminedichloroplatinum (II) in a rat ovarian carcinoma cell line.
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.
Sekiya
S
S
Department of Obstetrics and Gynceology, Chiba University School of Medicine, Japan.
Oosaki
T
T
Andoh
S
S
Suzuki
N
N
Akaboshi
M
M
Takamizawa
H
H
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002945:Cisplatin / Q000627:therapeutic use*; D004260:DNA Repair; D004351:Drug Resistance; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007621:Karyotyping; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D005978:Glutathione; D002945:Cisplatin