Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines.
The formation and removal of four platinum-DNA adducts were immunochemically quantitated in cultured cells derived from a human bladder carcinoma cell line (RT112) and from two lines derived from germ cell tumors of the testis (833K and SUSA), following exposure in vitro to 16.7 microM (5 micrograms/ml) cisplatin. RT112 cells were least sensitive to the drug and were proficient in the repair of all four adducts, whereas SUSA cells, which were 5-fold more sensitive, were deficient in the repair of DNA-DNA intrastrand cross-links in the sequences pApG and pGpG. Despite expressing a similar sensitivity to SUSA cells, 833K cells were proficient in the repair of all four adducts, although less so than the RT112 bladder tumor cells. In addition, SUSA cells were unable to repair DNA-DNA interstrand cross-links whereas 50-85% of these lesions were removed in RT112 and 833K cells 24 h following drug exposure. It is possible that the inability of SuSa cells to repair platinated DNA may account for their hypersensitivity to cisplatin.
Bedford
P
P
Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London, United Kingdom.
Fichtinger-Schepman
A M
AM
Shellard
S A
SA
Walker
M C
MC
Masters
J R
JR
Hill
B T
BT
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology; D004260:DNA Repair; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D010984:Platinum / Q000378:metabolism*; D011868:Radioisotopes; D013736:Testicular Neoplasms / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D004273:DNA, Neoplasm; D011868:Radioisotopes; D010984:Platinum; D002945:Cisplatin