Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA.
Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, we identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair.
Chu
G
G
Department of Medicine, Stanford University School of Medicine, CA 94305.
Chang
E
E
D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects* / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004351:Drug Resistance; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D002945:Cisplatin