EXCISION-REPAIR CROSS-COMPLEMENTING RODENT REPAIR DEFICIENCY GENE-2 EXPRESSION AND CHLOROETHYLNITROSOUREA RESISTANCE IN HUMAN GLIOMA CELL-LINES

OBJECTIVE: Nitrosoureas are the standard chemotherapeutic agents for m alignant brain tumors. However, their anticancer effects are limited b ecause many tumors are resistant to these agents. Nucleotide excision repair can repair bulky deoxyribonucleic acid adducts, including deoxy ribonucleic acid damage induced by ultraviolet light and some chemothe rapeutic agents, and may be implicated in nitrosoureas resistance. In this study, we compared excision repair cross-complementing rodent rep air deficiency Gene 2 (ERCC2), an important component of the nucleotid e excision repair system, with 1,3-bis-(2-chloroethyl)-1-nitrosourea o r (2-chloroethyl)-3-sarcosinamide-1-nitrosourea resistance in human gl ioma cell lines. METHODS: ERCC2 expression was evaluated by using esta blished quantitative reverse-transcription polymerase chain reaction. 1,3-Bis-(2-chloroethyl)-1-nitrosourea and (2-chloroethyl)-3-sarcosinam ide-1-nitrosourea cytotoxicity were determined by a modification of th e sulforhodamine B colorimetric anticancer drug screening assay. RESUL TS: A significant correlation between ERCC2 expression and 1,3-bis-(2- chloroethyl)-1-nitrosourea or (2-chloroethyl)-3-sarcoinamide-1-nitroso urea cytotoxicity was determined (r = 0.737, P = 0.0226 and r = 0.789, P = 0.0113, respectively). CONCLUSION: Our results suggest that nucle otide excision repair, specifically ERCC2, may play an important role in nitrosoureas drug resistance in human gliomas.