Arylamines DNA adduct (environmental carcinogens)

Arylamines belong to an important class of environmental carcinogens which are implicated in the etiology of many human cancers. 2-Aminofluorene and its derivatives are prototype arylamine carcinogens that form two DNA adducts in vivo: AF and AAF. AF is the major and most persistent adduct. It is known to exist in a sequence-dependent equilibrium between external B-type and stacked S-conformers, as defined by the location (major groove and base-displaced, respectively) of the carcinogen moiety. A minor groove binding wedged (W)-conformer has also been observed in duplexes in which the lesion is mismatched with purine bases. The dynamics of the AF-induced B/S/W-heterogeneity have been shown to be modulated by both the base sequence contexts and the progression for the length of primers, and contribute to polymerase activity through a long-range effect. The sequence effects on adduct conformation and the nature of the polymerase are key factors for determining the mutational outcomes of these important carcinogens. This animation shows the rotating views of the external B-type (B), base-displaced stacked (S), minor groove wedge (W)-conformers. The modified dG and the complementary dC are shown in cyan and green CPK, respectively, and the aminofluorene carcinogen moiety is highlighted with red CPK.




Nathan Haskins/Dr. Bongsup Cho

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• maya
• neight
• nhaskins
• arylamines
• science
• visulization
• cho
• URI
• environmental
• carcinogens