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    Heterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment.

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    Authors
    Lees, Nicholas P
    Harrison, Kathryn L
    Hill, Elizabeth
    Hall, C Nicholas
    Povey, Andrew C
    Margison, Geoffrey P
    Affiliation
    Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, UK.
    Issue Date
    2002
    
    Metadata
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    Abstract
    OBJECTIVES: MGMT (O(6)-alkylguanine-DNA alkyltransferase) reverses the carcinogenic, mutagenic and cytotoxic effects of alkylating agents. Measurement of MGMT activity in tumours might thus be of use in selecting those patients with colorectal cancer who may be sensitive to adjuvant alkylating agent therapy. The aim of this study was to assess whether measurement of MGMT activity in a single tumour biopsy is representative of the whole tumour. METHODS: Multiple symmetrically spaced biopsies were taken from colorectal cancers obtained from 9 patients. MGMT activity was then measured in cell-free extracts by quantifying the transfer of [(3)H]methyl group from calf thymus DNA methylated in vitro with N-nitroso-N-[(3)H]-methylurea to the MGMT protein. RESULTS: MGMT activity was detected in all tumour samples with the activity ranging between 3.6 and 36.2 fmol/microg DNA and 202-1,986 fmol/mg protein. Heterogeneity in MGMT activity (ratio of maximum/minimum MGMT levels per tumour) varied between 1.3 and 5.4. CONCLUSIONS: Measurement of MGMT activity in a single biopsy is not necessarily indicative of the level throughout the tumour. The response of colorectal cancers to alkylating agent treatment is likely to be non-uniform both within the tumour and between patients.
    Citation
    Heterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment. 2002, 63 (4):393-7 Oncology
    Journal
    Oncology
    URI
    http://hdl.handle.net/10541/82467
    DOI
    10.1159/000066221
    PubMed ID
    12417795
    Type
    Article
    Language
    en
    ISSN
    0030-2414
    ae974a485f413a2113503eed53cd6c53
    10.1159/000066221
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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