[Isolation of cisplatin-resistant subline from human ovarian cancer cell line and analysis of its cell-biological characteristics].
The cisplatin (CDDP)-resistant subline TYK-nu (R) was developed by culturing TYK-nu (human ovarian cancer cell line in vitro) with exposure to CDDP in stepwise increasing concentrations. The characteristics of both cell lines were compared and the results were as follows; 1. Both cell lines formed a monolayer in a pavement-like arrangement and large cells were occasionally present in TYK-nu (R) rather than TYK-nu. The population doubling time of TYK-nu and TYK-nu (R) was 43 hr and 48 hr, respectively. 2. IC50 (microgram/ml) in 96 hr treatment with CDDP and carboplatin (CBDCA) was 0.035 and 0.5 in TYK-nu and 0.62 and 2.0 in TYK-nu (R), respectively. 3. In the intracellular CDDP concentration, there was no marked difference between TYK-nu and TYK-nu (R) after CDDP (2.0 micrograms/ml) treatment in 2hr. 4. After treatment with CDDP (0.2 microgram/ml) or CBDCA (2.0 micrograms/ml), a decrease in S and G2 + M compartments was observed in the pattern of the DNA histogram of TYK-nu, but not in that of TYK-nu (R). 5. The majority of chromosomes in both cell lines were in hyperdiploid areas and the mode of TYK-nu and TYK-nu (R) was 56 and 51, respectively. The karyotype of TYK-nu (R) showed deletion of chromosome 7q. Thus, compared to TYK-nu, TYK-nu (R) was 17.7 times more resistant to CDDP and 4 times more resistant to CBDCA. The results suggest that the mechanism of resistance to CDDP may be due to genetic changes at the cellular level.
Yoshiya
N
N
Department of Obstetrics and Gynecology, School of Medicine, Niigata University.
Adachi
S
S
Misawa
Y
Y
Yuzawa
H
H
Honda
T
T
Kanazawa
K
K
Takeuchi S Tanaka
K
K
Tanaka
K
K
D016190:Carboplatin; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D004171:Diploidy; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007621:Karyotyping; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D016190:Carboplatin; D002945:Cisplatin