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    Stability and capacity of dimethylnitrosamine-induced O6-methylguanine repair system in rat liver.

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    Authors
    Montesano, R
    Brésil, H
    Planche-Martel, G
    Margison, Geoffrey P
    Pegg, A E
    Affiliation
    IARC, 69372 Lyon Cedex, France
    Issue Date
    1983-12
    
    Metadata
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    Abstract
    Repeated administration of dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) to BD IV rats results in an increased capacity for the liver to repair O6-methylguanine in DNA, whereas other DNA adducts (7-methylguanine and 3-methyladenine) are not affected. In the experiments reported here, data on the rapidity of action of the enhanced system, its capacity after different challenging doses of [14C]DMN (0.2, 2.0, and 20 mg/kg), and the persistence after cessation of the DMN pretreatment are described. The results show that, after a dose of [14C]DMN (2.0 mg/kg), the increased activity acts very rapidly (10 min) repairing O6-methylguanine as soon as it is formed and that, by 2 hr, 65% of the O6-methylguanine generated in liver DNA has already been removed. Very little removal of O6-methylguanine occurs within this time in control rats not receiving any DMN pretreatment. The DMN-induced repair activity is of limited capacity, since its effect can be detected after DNA damage induced by 0.2 or 2.0 mg of [14C]DMN per kg, whereas this activity has little impact on the O6-methylguanine generated in liver DNA by 20 mg of [14C]DMN per kg. Upon cessation of the DMN pretreatment, the enhanced repair activity, as determined also by the in vitro activity of the O6-methyltransferase, decays slowly, but after 25 days, the repair activity is still higher than control values. No correlation was observed between increased [3H]thymidine incorporation in liver DNA and increased O6-methylguanine repair, indicating that liver cell proliferation is not necessarily coupled with an elevated methyltransferase level.
    Citation
    Stability and capacity of dimethylnitrosamine-induced O6-methylguanine repair system in rat liver. 1983, 43 (12 Pt 1):5808-14 Cancer Res
    Journal
    Cancer Research
    URI
    http://hdl.handle.net/10541/337919
    PubMed ID
    6640532
    Type
    Article
    Language
    en
    ISSN
    0008-5472
    Collections
    All Paterson Institute for Cancer Research

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