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

2.50
Hdl Handle:
http://hdl.handle.net/10541/100092
Title:
Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase.
Authors:
Brent, T P; Von Wronski, M A; Edwards, C C; Bromley, Michael; Margison, Geoffrey P; Rafferty, Joseph A; Pegram, C N; Bigner, D D
Abstract:
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.
Affiliation:
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN.
Citation:
Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase. 1993, 5 (2):83-6 Oncol. Res.
Journal:
Oncology Research
Issue Date:
1993
URI:
http://hdl.handle.net/10541/100092
PubMed ID:
8364257
Type:
Article
Language:
en
ISSN:
0965-0407
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBrent, T Pen
dc.contributor.authorVon Wronski, M Aen
dc.contributor.authorEdwards, C Cen
dc.contributor.authorBromley, Michaelen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorPegram, C Nen
dc.contributor.authorBigner, D Den
dc.date.accessioned2010-06-01T16:20:22Z-
dc.date.available2010-06-01T16:20:22Z-
dc.date.issued1993-
dc.identifier.citationIdentification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase. 1993, 5 (2):83-6 Oncol. Res.en
dc.identifier.issn0965-0407-
dc.identifier.pmid8364257-
dc.identifier.urihttp://hdl.handle.net/10541/100092-
dc.description.abstractCellular 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.en
dc.language.isoenen
dc.subjectCancer Transplantationen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals-
dc.subject.meshCell Nucleus-
dc.subject.meshDrug Resistance-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMethyltransferases-
dc.subject.meshMice-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshNeoplasm Transplantation-
dc.subject.meshNitrosourea Compounds-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshRhabdomyosarcoma-
dc.subject.meshTransplantation, Heterologous-
dc.subject.meshTumor Cells, Cultured-
dc.titleIdentification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase.en
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN.en
dc.identifier.journalOncology Researchen

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