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Individual differences in DNA repair capacities in man.

F Oesch, W Aulmann, K L Platt

    Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement
    |January 1, 1987
    PubMed
    Summary

    Large variations in DNA repair capacity for benzo[a]pyrene DNA adducts were observed among individuals. Some people showed a complete lack of repair, while smokers generally had lower adduct levels, except for one individual with impaired repair.

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    The nucleotide excision repair protein XPC is essential for bulky DNA adducts to promote interleukin-6 expression via the activation of p38-SAPK.

    Oncogene·2015

    Area of Science:

    • Environmental Carcinogenesis
    • Molecular Toxicology
    • DNA Repair Mechanisms

    Background:

    • Benzo[a]pyrene is metabolically activated to a potent carcinogen, benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide.
    • This ultimate carcinogen forms DNA adducts, primarily binding to the exocyclic amino group of guanine.

    Purpose of the Study:

    • To investigate interindividual differences in the repair capacity of DNA adducts formed by benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide.
    • To assess the persistence of these DNA adducts in lymphocytes from different donors.

    Main Methods:

    • Analysis of DNA adduct formation and persistence in freshly isolated lymphocytes from multiple donors.
    • Comparison of adduct levels between smokers and non-smokers.
    • Investigation of DNA repair of methylnitrosourea-induced lesions.

    Main Results:

    • Significant interindividual variation in DNA adduct formation and persistence was observed.
    • Several individuals exhibited a complete lack of repair capability for these specific adducts.
    • Smokers generally showed lower initial adduct levels, suggesting enzyme induction, but one smoker had impaired repair.
    • Interindividual differences in adaptive DNA repair response were noted for methylnitrosourea, but variations after single doses were minimal.

    Conclusions:

    • Individual susceptibility to benzo[a]pyrene carcinogenicity can be influenced by variations in DNA repair capacity.
    • The study highlights the importance of considering interindividual differences in DNA repair when assessing cancer risk from environmental carcinogens.
    • Combined exposure to carcinogens and impaired DNA repair presents a significant risk, as exemplified by the studied smoker.

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