Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells.
The resistance of tumor cells to chemotherapeutic agents, such as cisplatin,is an important problem to be solved in cancer chemotherapy. One of the mechanisms associated with cisplatin resistance is nucleotide excision repair (NER). There are two pathways in NER, transcription-coupled NER (TC-NER) and global genome NER (GG-NER). Here, we report that TC-NER-deficient cells [xeroderma pigmentosum group A (XP-A), XP-D, XP-F, XP-G, Cockayne syndrome group A (CS-A), and CS-B] are hypersensitive to cisplatin irrespective of their GG-NER status, and that gene complementation with XPA and XPD increases resistance to cisplatin. By contrast, XP-C cells with selective defect in GG-NER but with normal TC-NER have normal resistance to cisplatin. XPC complementation had no effect on cisplatin antiproliferative activity. We propose that one of the pathways related to cisplatin response is TC-NER, not GG-NER.
Furuta
Takahisa
T
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA.
Ueda
Takahiro
T
Aune
Gregory
G
Sarasin
Alain
A
Kraemer
Kenneth H
KH
Pommier
Yves
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000494:pharmacology*; D004260:DNA Repair / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000473:pathology
D000970:Antineoplastic Agents; D002945:Cisplatin