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    Effects of 5-methylnicotinamide on mouse L1210 cells exposed to N-methyl-N-nitrosourea: mutation induction, formation and removal of methylation products in DNA, and unscheduled DNA synthesis.

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    Authors
    Durrant, L G
    Margison, Geoffrey P
    Boyle, John M
    Affiliation
    Paterson Laboratories, Christie Hospital and Holt Radiium Institute, Manchester, M20 9BX, UK.
    Issue Date
    1981
    
    Metadata
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    Abstract
    The lethality of N-methyl-N-nitrosourea (MNU) to mouse L1210 cells, as determined by colon forming ability, was potentiated 2.8 fold by the addition of 1 mM 5'-methylnicotinamide (5MeN). When 5MeN was present throughout the expression and selection of 6-thioguanine resistant mutants, the MNU-induced mutation frequency was reduced in duplicate experiments from 15.6 and 12.0 to 7.0 mutants per 10(4) survivors per mM MNU. At the same level of survival, cells treated with 5MeN had approximately 12 times fewer mutants than untreated cells. The rate of removal of the promutagenic lesion O6-methylguanine from DNA was enhanced approximately 2-fold, whereas that of 7-methylguanine was unaffected by the incubation of MNU treated cells with 5MeN. Since 5MeN is a potent inhibitor of poly(ADP-ribose) polymerase, this may imply that in normal cells it is specific ADP-ribosylation of the repair enzyme causing the removal of O6-methylguanine, rather than a more general modification of chromatin structure, that limits the rate of repair of the promutagenic lesion. 5MeN also stimulated unscheduled DNA synthesis in MNU treated cells, implying that an earlier observation that 5MeN prevented rejoining of strand breaks induced by repair of alkyl lesions, probably resulted from inhibition of ligation and not the failure of DNA polymerase to replace bases removed by repair nucleases.
    Citation
    Effects of 5-methylnicotinamide on mouse L1210 cells exposed to N-methyl-N-nitrosourea: mutation induction, formation and removal of methylation products in DNA, and unscheduled DNA synthesis. 1981, 2 (10):1013-7 Carcinogenesis
    Journal
    Carcinogenesis
    URI
    http://hdl.handle.net/10541/134134
    DOI
    10.1093/carcin/2.10.1013
    PubMed ID
    6457699
    Type
    Article
    Language
    en
    ISSN
    0143-3334
    EISSN
    1460-2180
    ae974a485f413a2113503eed53cd6c53
    10.1093/carcin/2.10.1013
    Scopus Count
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    All Paterson Institute for Cancer Research

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