N-2-fluorenylacetamide-induced conformational and functional damage to DNA

Conformational and functional changes induced in DNA by N-2-fluorenylacetamide (2-FAA) modification are described. The carcinogen was bound to the C-8 and to N(2) positions of guanosine (G) residues and also formed a deacetylated N-2-fluorenamine (2-FA) adduct. Modification of G residues at the C-8 position caused a large conformational distortion in DNA expressed in a "base displacement model." According to this model, the G residue rotated from the preferred anti to syn positions, and the bulky 2-FAA residue was inserted into the DNA helix and displaced the G residue. The conformational distortion in DNA was detectable by single-strand specific S(1) nuclease digestion. On the other hand, substitution of 2-FAA on the N(2) position of G did not produce a major change in conformation of the DNA helix, and this was not recognized by S(1) nuclease splitting. On the basis of circular dichroism, proton magnetic resonance, and S(1) nuclease digestion data, it seemed that 2-FA-induced damage to DNA was less than that induced by 2-FAA modification of G at the C-8 position. Finally, effects induced by 2-FAA on RNA synthesis in vitro and in vivo systems and the possible relationship between the repair mechanisms and conformational damage of DNA are discussed.