Influence of the carcinogen 4-aminobiphenyl on DNA conformation.
The conformation of the deoxydinucleoside monophosphate dCpdG modified by the carcinogen 4-aminobiphenyl has been elucidated by minimized semi-empirical potential energy calculations. The most important conformers relevant to A or B and Z helices are shown, and the structures of carcinogen-modified polymers, obtained from computer-generated models that incorporate the dimer conformations, are presented. Forms with carcinogen-base stacking and with base-base stacking are found, for both A-B type helices and Z-type helices. In random sequence DNA, the most favored state places the carcinogen at the A or B helix exterior, in the large groove, where it causes no distortion. In this position it might escape repair till a round of replication. At the replication fork, where the DNA is unwound, a low energy carcinogen-base stacked state, easily achieved by rotation primarily about the C5' - O5' bond, could occur. A mutagenic outcome resulting from this conformation might be envisioned.
D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D002273:Carcinogens; D004247:DNA; D009690:Nucleic Acid Conformation / Q000187:drug effects*
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; C006757:4-biphenylamine; D004247:DNA