Chemical and biological factors affecting mutagen potency

This review surveys the chemical and biological factors that are correlated with the mutagenic activity of the aromatic and heterocyclic amines. Particular attention is given to the predicted quantum chemical properties of the parent amines and their metabolites. A number of chemical properties have been found to correlate well with measured mutagenic potency, including log P, the energies of the frontier orbitals of the parent amines, and the thermodynamic stability of the nitrenium ion, possibly the ultimate DNA-binding species. These correlations are intriguing clues to the mutagenic activity of the aromatic amines; however, many factors still await final explanation, including the exact mechanisms of the metabolic enzymes, the identity(s) of the ultimate DNA-binding species, the reaction mechanism in the DNA-adduction, the role of sequence context in the covalent and non-covalent binding of the adducts, and the role of DNA repair.