In vitro reaction of the carcinogenic derivative N-acetoxy-7-ethyl-N-2-acetylaminofluorene with DNA. A spectroscopic study.

In vitro reaction of DNA with N-acetoxy-7-ethyl-N-acetylaminofluorene (N-AcO-EtAAF is compared to that with N-acetoxy-N-acetyl-2-aminofluorene. Introduction of an ethyl group at the position 7 of the fluorene ring is found to induce an increase of reactivity of this (model) metabolite of carcinogen N-acetoxy-2-aminofluorene (2-AAF) toward DNA and its constituents. Spectroscopic methods (u.v. absorption and circular dichroism) are used to characterize the DNA reacted with N-AcO-EtAAF (DNA-EtAAF). Our results point out some conformational similarities between native DNA-EtAAF and DNA-AAF such as the presence of destabilized regions around the bound carcinogen and of stacking interactions between these residues and the adjacent nucleotides. Quite important differences seem to exist between adducts or modified sequences in native as compared to denatured DNA (contrary to DNA-AAF and DNA bearing covalently bound-2-aminofluorene.