Computer-generated graphic models of the N2-substituted deoxyguanosine adducts of 2-acetylaminofluorene and benzo[a]pyrene and the O6-substituted deoxyguanosine adduct of 1-naphthylamine in the DNA double helix.
Computer models of three deoxyguanosine-carcinogen adducts in double-helical DNA are presented. The carcinogen moiety is rotated and the best fit within the double helix is evaluated. The 2-acetylaminofluorene (AAF) derivative, 3-(deoxyguanosin-N2-yl)-AAF, is found to be situated within the minor groove, has very little freedom of rotation and causes little helical distortion. The (+)-anti-benzo[a]-pyrene (BP)-diol epoxide-N2 adduct, 10beta-(deoxyguanosin-N2-yl)-7beta, 8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydro-BP, has a similar fit with a greater degree of steric interaction, suggesting that this adduct could cause some local destabilization. The 1-naphthylamine (NA) derivative, N1-(deoxyguanosine-O6-yl)-1-NA, resides within the major groove, does not perturb the helix and has considerable freedom of movement.
D015057:1-Naphthylamine / Q000378:metabolism*; D015073:2-Acetylaminofluorene / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism*; D003201:Computers; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism*; D008958:Models, Molecular; D009281:Naphthalenes / Q000378:metabolism*; D009690:Nucleic Acid Conformation
D001580:Benzopyrenes; D005449:Fluorenes; D009281:Naphthalenes; D004247:DNA; D015057:1-Naphthylamine; D015073:2-Acetylaminofluorene; D003849:Deoxyguanosine