EXPRESSION OF GENES INVOLVED IN NUCLEOTIDE EXCISION-REPAIR AND SENSITIVITY TO CISPLATIN AND MELPHALAN IN HUMAN CANCER CELL-LINES

DNA repair has been proposed to be an important determinant of cancer cell sensitivity to alkylating agents and cisplatin (DDP). Nucleotide excision repair (NER), which represents one of the most important cell ular DNA repair processes able to remove a broad spectrum of DNA lesio ns, is involved in the recognition and repair of the crosslinks caused by DDP and melphalan (L-PAM). In this study, the mRNA levels of the d ifferent genes involved in NER (ERCC1, XPA, XPB, XPC, XPD, XPF) were e xamined in a panel of eight different human cancer cell lines, togethe r with the overall DNA repair capacity using a host cell reactivation assay of a damaged plasmid. A statistically significant correlation wa s observed between the relative expression of XPA/XPC (P < 0.05) and E RCC1/XPC (P < 0.05) mRNAs. No correlation was found between the DDP an d L-PAM. IC50S and the relative mRNA expression of the tested NER gene s. When the overall cellular DNA repair capacity was studied, carcinom as seemed to have a higher repair activity than leukaemias; but this r epair DNA activity correlated neither with the mRNA expression of the different NER genes nor with DDP and L-PAM IC(50)s. These data seem to suggest that even if the NER pathway is an important determinant for the cytotoxicity of alkylating agents, as demonstrated by the extremel y high sensitivity to alkylating agents in cells lacking this repair s ystem, other factors have to play a role in regulating the cellular se nsitivity/resistance to these antitumour drugs. (C) 1998 Elsevier Scie nce Ltd. All rights reserved.