Mechanism of C8 alkylation of guanine residues by activated arylamines: evidence for initial adduct formation at the N7 position

Numerous C8 substituted guanine derivations were reacted with N-acetoxy-2-aminofluorene prepared in situ from 2-acetylsalicylic acid and N-hydroxy-2-aminofluorene to determine whether the C8 adduct is the final product after initial N7 adduct formation. An initial electrophilic substitution of the N7 atom, believed to be a general reaction for stimulated arylamines and heterocyclic amines, precedes C8 adduct formation. Electrophilic compounds that react with DNA are bioactivated by aromatic amines, primarily at the C8 position of guanine bases.