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    Formation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay.

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    Authors
    Jackson, Peta E
    Cooper, Donald P
    Meyer, T A
    Wood, M
    Povey, Andrew C
    Margison, Geoffrey P
    Affiliation
    CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
    Issue Date
    2000-06-05
    
    Metadata
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    Abstract
    Female SWR mice were treated with 1,2-dimethylhydrazine (DMH: 6.8 mg/kg i.p. injection) once weekly for up to 10 weeks, a dosing regime that produced tumours principally within the distal colon (Jackson et al., 1999. Carcinogenesis 20, 509-513). O(6)-Methylguanine (O(6)-MeG) levels, measured using a simple [3H]-based O(6)-alkylguanine-DNA alkyltransferase (ATase) inactivation assay, ranged from 0.6 to 16.7 fmol/microg DNA with: (i) highest levels in the distal colon; and (ii) higher levels after 68 mg/kg total DMH than 6.8 mg/kg DMH. Basal ATase activity varied between 0.97 and 1.22 fmol/microg DNA within the colon but was not associated with adduct levels or tumour induction. After 6.8 mg/kg DMH, the half life of O(6)-MeG in colonic tissue was 36-42 h whereas after 68 mg/kg DMH, t1/2 was approximately 25, 57 and 96 h in the proximal, mid and distal colon, respectively. Tumour induction was thus associated with the levels and persistence of O(6)-MeG in the distal colon.
    Citation
    Formation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay. 2000, 115 (3):205-12 Toxicol. Lett.
    Journal
    Toxicology Letters
    URI
    http://hdl.handle.net/10541/88617
    DOI
    10.1016/S0378-4274(00)00193-4
    PubMed ID
    10814890
    Type
    Article
    Language
    en
    ISSN
    0378-4274
    ae974a485f413a2113503eed53cd6c53
    10.1016/S0378-4274(00)00193-4
    Scopus Count
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    All Paterson Institute for Cancer Research

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