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

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    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
    Affiliation
    Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN.
    Issue Date
    1993
    
    Metadata
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    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.
    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
    URI
    http://hdl.handle.net/10541/100092
    PubMed ID
    8364257
    Type
    Article
    Language
    en
    ISSN
    0965-0407
    Collections
    All Paterson Institute for Cancer Research

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