Excision repair cross-complementing rodent repair deficiency gene 2 expression and chloroethylnitrosourea resistance in human glioma cell lines

Neurosurgery. 1998 May;42(5):1112-9. doi: 10.1097/00006123-199805000-00094.

Abstract

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).

Conclusion: Our results suggest that nucleotide excision repair, specifically ERCC2, may play an important role in nitrosoureas drug resistance in human gliomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Carmustine / analogs & derivatives*
  • Carmustine / pharmacology*
  • Colorimetry
  • DNA Helicases*
  • DNA Repair / genetics*
  • DNA, Neoplasm / genetics*
  • DNA-Binding Proteins*
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genetic Complementation Test
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Proteins / genetics*
  • Transcription Factors*
  • Tumor Cells, Cultured
  • Xeroderma Pigmentosum Group D Protein

Substances

  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Proteins
  • Transcription Factors
  • 2-((((2-chloroethyl)nitrosoamino)carbonyl)amino)propanamide
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Carmustine