• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • 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

    Reduced MGMT activity in human colorectal adenomas is associated with K-ras GC->AT transition mutations in a population exposed to methylating agents.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Lees, Nicholas P
    Harrison, Kathryn L
    Hall, C Nicholas
    Margison, Geoffrey P
    Povey, Andrew C
    Affiliation
    Department of Gastrointestinal Surgery, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK.
    Issue Date
    2004-07
    
    Metadata
    Show full item record
    Abstract
    There is increasing evidence to suggest that O(6)-alkyl guanine DNA-alkyltransferase (MGMT) activity provides protection against alkylating agent induced formation of GC-->AT transition mutations in the K-ras oncogene of colorectal tumours. As this mutagenic event occurs during the growth of adenomas, both biomarkers of exposure (N7-methylguanine levels in DNA) and susceptibility (MGMT activity) were measured in biopsy samples obtained from normal and adenomatous tissue from 34 patients with large adenomas (>10 mm in size). There was no correlation between MGMT activity in the adenoma and in matched normal tissue. However, MGMT activity was significantly lower in adenoma tissue than in adjacent normal mucosa (5.18 versus 7.05 fmol/microg DNA, P = 0.01), particularly in men and those whose age was greater than the median. Upon stratification by K-ras mutational status, MGMT activity was lower in adenomas bearing a K-ras GC-->AT transition mutation (mean 4.21 fmol/microg DNA) than in adjacent normal tissue (mean 7.7 fmol/microg DNA; P < 0.004). In contrast, there was no significant difference in MGMT activity in adenomas lacking a K-ras GC-->AT transition mutation and adjacent normal mucosa. N7-methylguanine levels however did not vary with age, gender, K-ras mutational status or MGMT activity. These results are consistent with the acquisition of K-ras GC-->AT transition mutations in adenomas with low MGMT activity as a result of unavoidable exposure to methylating agents.
    Citation
    Reduced MGMT activity in human colorectal adenomas is associated with K-ras GC->AT transition mutations in a population exposed to methylating agents. 2004, 25 (7):1243-7 Carcinogenesis
    Journal
    Carcinogenesis
    URI
    http://hdl.handle.net/10541/78138
    DOI
    10.1093/carcin/bgh111
    PubMed ID
    14963016
    Type
    Article
    Language
    en
    ISSN
    0143-3334
    ae974a485f413a2113503eed53cd6c53
    10.1093/carcin/bgh111
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Human colorectal mucosal O6-alkylguanine DNA-alkyltransferase activity and DNA-N7-methylguanine levels in colorectal adenoma cases and matched referents.
    • Authors: Lees NP, Harrison KL, Hall CN, Margison GP, Povey AC
    • Issue date: 2007 Mar
    • Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis.
    • Authors: Esteller M, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Watkins DN, Issa JP, Sidransky D, Baylin SB, Herman JG
    • Issue date: 2000 May 1
    • DNA alkylation and repair in the large bowel: animal and human studies.
    • Authors: Povey AC, Badawi AF, Cooper DP, Hall CN, Harrison KL, Jackson PE, Lees NP, O'Connor PJ, Margison GP
    • Issue date: 2002 Nov
    • Low O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene.
    • Authors: Jackson PE, Hall CN, O'Connor PJ, Cooper DP, Margison GP, Povey AC
    • Issue date: 1997 Jul
    • Reduced lung tumorigenesis in human methylguanine DNA--methyltransferase transgenic mice achieved by expression of transgene within the target cell.
    • Authors: Liu L, Qin X, Gerson SL
    • Issue date: 1999 Feb
    DSpace software (copyright © 2002 - 2023)  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.