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dc.contributor.authorBrent, T P
dc.contributor.authorVon Wronski, M A
dc.contributor.authorEdwards, C C
dc.contributor.authorBromley, Michael
dc.contributor.authorMargison, Geoffrey P
dc.contributor.authorRafferty, Joseph A
dc.contributor.authorPegram, C N
dc.contributor.authorBigner, D D
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.
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
html.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.


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