DNA Modification in Vitro and in Vivo withHeterocyclic Amines
Physicochemical affinity of mutagens to DNA is thought to facilitate covalent bindings with DNA, because molecules which interact with DNA should covalently bind to DNA more easily than free molecules. Pezzuto et al. synthesized Trp-P-2. Trp-P-1, and their derivatives, which showed various degrees of mutagenicity toward Salmonella typhimurium in the presence of the microsomal activation system. The nature of the DNA affinity of heterocyclic amines has been studied with the use of a closed circular DNA. Nonmutagenic heterocyclic amines, harman and norharman, were the first that were shown to unwind superhelical plasmid DNA. The DNA adducts formed in rats in vivo on treatment intragastrically with 50 mg/kg of MelQx, Glu-P-1, or Trp-P-1 were also analyzed by the postlabeling method. The products were compared to the adducts obtained from in vitro modification of DNA with MeIQx-NHOH, Glu-P-2-NHOH, or Trp-P-1-NHOH in the presence or absence of acetic anhydride.