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Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase.

Publication ,  Journal Article
Brent, TP; von Wronski, MA; Edwards, CC; Bromley, M; Margison, GP; Rafferty, JA; Pegram, CN; Bigner, DD
Published in: Oncol Res
1993

Cellular levels of O6-methylguanine-DNA methyltransferase (MGMT) correlate strongly with cellular resistance to carcinogenic and chemotherapeutic agents that produce adducts at the O6-position of guanine in DNA. Although biochemical and molecular assays can indicate the average MGMT content of tissues or tumors, they cannot distinguish mixed populations of cells, such as those that exist in tumor biopsy samples. We have determined MGMT at the cellular level in a panel of pediatric rhabdomyosarcoma xenografts by in situ immunostaining with a human MGMT-specific antibody employing a very sensitive procedure that involves biotin-avidin coupled horseradish peroxidase with silver-enhanced diaminobenzidine-nickel staining. Two xenograft tumor lines known to be MGMT-deficient were not stained, whereas the nuclei in three MGMT-expressing lines were clearly stained. This is the first demonstration of an in situ procedure that discriminates drug-sensitive MGMT-deficient tumors from drug-resistant MGMT expressing tumors. This procedure should prove useful, therefore, for predicting the susceptibility of tissues and tumors to O6-guanine alkylating agents.

Duke Scholars

Published In

Oncol Res

ISSN

0965-0407

Publication Date

1993

Volume

5

Issue

2

Start / End Page

83 / 86

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Rhabdomyosarcoma
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Nitrosourea Compounds
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Mice
  • Methyltransferases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brent, T. P., von Wronski, M. A., Edwards, C. C., Bromley, M., Margison, G. P., Rafferty, J. A., … Bigner, D. D. (1993). Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase. Oncol Res, 5(2), 83–86.
Brent, T. P., M. A. von Wronski, C. C. Edwards, M. Bromley, G. P. Margison, J. A. Rafferty, C. N. Pegram, and D. D. Bigner. “Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase.Oncol Res 5, no. 2 (1993): 83–86.
Brent TP, von Wronski MA, Edwards CC, Bromley M, Margison GP, Rafferty JA, et al. Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase. Oncol Res. 1993;5(2):83–6.
Brent TP, von Wronski MA, Edwards CC, Bromley M, Margison GP, Rafferty JA, Pegram CN, Bigner DD. Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase. Oncol Res. 1993;5(2):83–86.
Journal cover image

Published In

Oncol Res

ISSN

0965-0407

Publication Date

1993

Volume

5

Issue

2

Start / End Page

83 / 86

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Rhabdomyosarcoma
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Nitrosourea Compounds
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Mice
  • Methyltransferases