• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Relationships between the formation of O6-methyldeoxyguanosine by 1-p-carboxyl-3,3-dimethylphenyltriazene in DNA and O6-alkylguanine-DNA alkyltransferase in human peripheral leukocytes.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Lee, Siow Ming
    O'Connor, Peter J
    Thatcher, Nick
    Crowther, Derek
    Margison, Geoffrey P
    Cooper, Donald P
    Affiliation
    CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital, National Health Service Trust, Manchester, UK.
    Issue Date
    1994-08-01
    
    Metadata
    Show full item record
    Abstract
    There is increasing experimental evidence to indicate that O6-methyldeoxyguanosine (O6-MedG) formation in DNA is a critical cytotoxic event following exposure to certain antitumor alkylating agents and that the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) can confer resistance to these agents. We recently demonstrated a wide interindividual variation in the depletion and subsequent regeneration of ATase in peripheral blood lymphocytes of patients treated with 24-h continuous infusion of 1-p-carboxyl-3,3-dimethylphenyltriazene (CB10-277) for metastatic melanoma. We have now measured the formation of O6-MedG in the DNA of peripheral leukocytes of nine patients receiving this treatment regimen. This lesion could be detected in DNA within 1 h and a progressive increase in adduct levels occurred during the CB10-277 infusion and for 24 h after completion. Considerable interindividual variation was observed in the peak O6-MedG levels, with values ranging from 3.0 to 23.8 mumol O6-MedG/mol deoxyguanosine (mean, 12.3 +/- 6.4 mumol O6-MedG/mol deoxyguanosine) following the first treatment cycle, possibly as a consequence of differences in the capacity of patients to metabolize CB10-277 to a methylating agent. There was, nevertheless, a clear temporal relationship between the progressive formation of leukocyte O6-MedG and lymphocyte ATase depletion. Repeated-measures regression showed that this was statistically significant (P < 0.001) during the CB10-277 infusion. A significant inverse correlation was also seen between pretreatment lymphocyte ATase activity and peak O6-MedG levels in leukocyte DNA (r = -0.73) and the area under the leukocyte O6-MedG concentration-time curve (r = -0.76). Metabolism of CB10-277 to a methylating agent could be one factor that combines with DNA repair capacity to determine clinical response, because the two responses observed in this series occurred in the two patients with the highest leukocyte O6-MedG levels and also the lowest pretreatment ATase activity. Hematological toxicity developed in the same two patients.
    Citation
    Relationships between the formation of O6-methyldeoxyguanosine by 1-p-carboxyl-3,3-dimethylphenyltriazene in DNA and O6-alkylguanine-DNA alkyltransferase in human peripheral leukocytes. 1994, 54 (15):4072-6 Cancer Res.
    Journal
    Cancer Research
    URI
    http://hdl.handle.net/10541/96301
    PubMed ID
    8033139
    Type
    Article
    Language
    en
    ISSN
    0008-5472
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Formation and loss of O6-methyldeoxyguanosine in human leucocyte DNA following sequential DTIC and fotemustine chemotherapy.
    • Authors: Lee SM, Margison GP, Thatcher N, O'Connor PJ, Cooper DP
    • Issue date: 1994 May
    • In vivo depletion of O6-alkylguanine-DNA-alkyltransferase in lymphocytes and melanoma of patients treated with CB 10-277, a new DTIC analogue.
    • Authors: Lee SM, Thatcher N, Crowther D, Margison GP
    • Issue date: 1992
    • O6-alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine.
    • Authors: Lee SM, Thatcher N, Margison GP
    • Issue date: 1991 Jan 15
    • Accumulation of O6-methylguanine in human blood leukocyte DNA during exposure to procarbazine and its relationships with dose and repair.
    • Authors: Souliotis VL, Kaila S, Boussiotis VA, Pangalis GA, Kyrtopoulos SA
    • Issue date: 1990 May 1
    • [Modulation of the antitumor activity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosoure a by O(6)-methyl-2'-deoxyguanosine--a new inhibitor of O(6)-alkylguanine-DNA-alkyltransferase].
    • Authors: Dederer LIu, Sokolova IS, Bakhmedova AA, Miniker TD, Mel'nik SIa, Gorbacheva LB
    • Issue date: 1995 Sep
    DSpace software (copyright © 2002 - 2019)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.