Establishment and biochemical properties of cis-diamminedichloroplatinum(II)-resistant A549 lung cancer cells.
A 6.2-fold cis-diamminedichloroplatinum(II) (CDDP) resistant human lung cancer cell line (A549/CDDP5), which was capable of proliferating in the presence of 5 microM CDDP, was developed. Compared to the parent cell line, A549/CDDP5 subline had a significantly longer doubling time, increased population of S phase, enhanced sensitivity to 5-FU and elevated activities of dTMP synthase (EC 2.1.1.45) and thymidine kinase (EC 2.7.1.21) by 5.4- and 2.0-fold of the parent cells. These results suggest that the capacity of dTMP synthesis might have an important role in the acquisition of CDDP resistance of A549 cells.
Yamauchi
N
N
First Department of Internal Medicine, Kagawa Medical School, Japan.
Shiotani
T
T
Yamaji
Y
Y
Fujita
J
J
Hata
Y
Y
Irino
S
S
D002455:Cell Division / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004351:Drug Resistance; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D016196:S Phase / Q000187:drug effects; D013937:Thymidine Kinase / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D013940:Thymidylate Synthase; D013937:Thymidine Kinase; D002945:Cisplatin; D005472:Fluorouracil