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 malignant brain tumors. However, their anticancer effects are limited because many tumors are resistant to these agents. Nucleotide excision repair can repair bulky deoxyribonucleic acid adducts, including deoxyribonucleic acid damage induced by ultraviolet light and some chemotherapeutic agents, and may be implicated in nitrosoureas resistance. In this study, we compared excision repair cross-complementing rodent repair deficiency Gene 2 (ERCC2), an important component of the nucleotide excision repair system, with 1 ,3-bis-(2-chloroethyl)-1-nitrosourea or (2-chloroethyl)-3-sarcosinamide-1-nitrosourea resistance in human glioma cell lines.


METHODS
ERCC2 expression was evaluated by using established quantitative reverse-transcription polymerase chain reaction. 1,3-Bis-(2-chloroethyl)-1-nitrosourea and (2-chloroethyl)-3-sarcosinamide-1-nitrosourea cytotoxicity were determined by a modification of the sulforhodamine B colorimetric anticancer drug screening assay.


RESULTS
A significant correlation between ERCC2 expression and 1 ,3-bis-(2-chloroethyl)-1-nitrosourea or (2-chloroethyl)-3-sarcosinamide-1-nitrosourea cytotoxicity was determined (r=0.737, P=0.0226 and r=0.789, P=0.0113, respectively).


CONCLUSIONS
Our results suggest that nucleotide excision repair, specifically ERCC2, may play an important role in nitrosoureas drug resistance in human gliomas.
Chen
Z P
ZP
Division of Neurosurgery, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
McQuillan
A
A
Mohr
G
G
Panasci
L C
LC
D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002330:Carmustine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003124:Colorimetry; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005816:Genetic Complementation Test; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D051759:Xeroderma Pigmentosum Group D Protein
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D014157:Transcription Factors; C044565:2-((((2-chloroethyl)nitrosoamino)carbonyl)amino)propanamide; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002330:Carmustine