• 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 DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Alkylpurine-DNA-N-glycosylase knockout mice show increased susceptibility to induction of mutations by methyl methanesulfonate.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Elder, Rhoderick H
    Jansen, J G
    Weeks, Robert J
    Willington, Mark
    Deans, Bryan
    Watson, Amanda J
    Mynett, Kurt J
    Bailey, John
    Cooper, Donald P
    Rafferty, Joseph A
    Heeran, Mel C
    Wijnhoven, S W
    Van Zeeland, A A
    Margison, Geoffrey P
    Show allShow less
    Affiliation
    CRC Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester M20 4BX, United Kingdom. RElder@picr.man.ac.uk
    Issue Date
    1998-10
    
    Metadata
    Show full item record
    Abstract
    Alkylpurine-DNA-N-glycosylase (APNG) null mice have been generated by homologous recombination in embryonic stem cells. The null status of the animals was confirmed at the mRNA level by reverse transcription-PCR and by the inability of cell extracts of tissues from the knockout (ko) animals to release 3-methyladenine (3-meA) or 7-methylguanine (7-meG) from 3H-methylated calf thymus DNA in vitro. Following treatment with DNA-methylating agents, increased persistence of 7-meG was found in liver sections of APNG ko mice in comparison with wild-type (wt) mice, demonstrating an in vivo phenotype for the APNG null animals. Unlike other null mutants of the base excision repair pathway, the APNG ko mice exhibit a very mild phenotype, show no outward abnormalities, are fertile, and have an apparently normal life span. Neither a difference in the number of leukocytes in peripheral blood nor a difference in the number of bone marrow polychromatic erythrocytes was found when ko and wt mice were exposed to methylating or chloroethylating agents. These agents also showed similar growth-inhibitory effects in primary embryonic fibroblasts isolated from ko and wt mice. However, treatment with methyl methanesulfonate resulted in three- to fourfold more hprt mutations in splenic T lymphocytes from APNG ko mice than in those from wt mice. These mutations were predominantly single-base-pair changes; in the ko mice, they consisted primarily of AT-->TA and GC-->TA transversions, which most likely are caused by 3-meA and 3- or 7-meG, respectively. These results clearly show an important role for APNG in attenuating the mutagenic effects of N-alkylpurines in vivo.
    Citation
    Alkylpurine-DNA-N-glycosylase knockout mice show increased susceptibility to induction of mutations by methyl methanesulfonate. 1998, 18 (10):5828-37 Mol. Cell. Biol.
    Journal
    Molecular and Cellular Biology
    URI
    http://hdl.handle.net/10541/93018
    PubMed ID
    9742100
    Type
    Article
    Language
    en
    ISSN
    0270-7306
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Modulation of the toxic and mutagenic effects induced by methyl methanesulfonate in Chinese hamster ovary cells by overexpression of the rat N-alkylpurine-DNA glycosylase.
    • Authors: Calléja F, Jansen JG, Vrieling H, Laval F, van Zeeland AA
    • Issue date: 1999 Apr 6
    • Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine.
    • Authors: Hang B, Singer B, Margison GP, Elder RH
    • Issue date: 1997 Nov 25
    • The effect of dietary folic acid deficiency on the cytotoxic and mutagenic responses to methyl methanesulfonate in wild-type and in 3-methyladenine DNA glycosylase-deficient Aag null mice.
    • Authors: Branda RF, O'Neill JP, Brooks EM, Powden C, Naud SJ, Nicklas JA
    • Issue date: 2007 Feb 3
    • Tobacco BY-2 cells excise both 3-methyladenine and 7-methylguanine from methylated DNA.
    • Authors: Kraszewska E, Dobrzańska M, Tudek B
    • Issue date: 1998 Nov 12
    • Spectrum of mutations induced by methyl and ethyl methanesulfonate at the hprt locus of normal and tag expressing Chinese hamster fibroblasts.
    • Authors: Klungland A, Laake K, Hoff E, Seeberg E
    • Issue date: 1995 Jun
    DSpace software (copyright © 2002 - 2025)  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.