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    Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide.

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    Authors
    Lee, S M
    Thatcher, Nick
    Crowther, Derek
    Margison, Geoffrey P
    Affiliation
    CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
    Issue Date
    1994-03
    
    Metadata
    Show full item record
    Abstract
    O6-alkylguanine-DNA-alkyltransferase (ATase) activity was measured in extracts of peripheral blood mononuclear cells (PMCs) taken from eight patients at various times during 5 days of oral treatment with temozolomide (150 mg m-2, days 1-5). Pretreatment ATase levels ranged from approximately 70 to 600 fmol per mg of protein. Depletion of PMC ATase was seen within 4 h of the first dose of temozolomide and had a median nadir of 52.9% and values ranging from 44.4% to 71.0% of pretreatment levels. There was a correlation between the extent of ATase depletion (pretreatment minus nadir level) and the pretreatment ATase level (r = 0.97). A progressive depletion of ATase was observed during the 5 days of continuous temozolomide therapy with median ATase activities of 66.3%, 52.5%, 39.5%, 30.5% and 28.9% of the pretreatment values at days 2, 3, 4, 5 and 6 respectively. This suggests that the schedule-dependent anti-tumour activity of temozolomide seen in experimental models and clinics may be related to a cumulative depletion of ATase.
    Citation
    Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. 1994, 69 (3):452-6 Br. J. Cancer
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/96519
    PubMed ID
    8123472
    PubMed Central ID
    1968858
    Type
    Article
    Language
    en
    ISSN
    0007-0920
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

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