CHEMICAL AND BIOLOGICAL FACTORS AFFECTING MUTAGEN POTENCY

This review surveys the chemical and biological factors that are corre lated with the mutagenic activity of the aromatic and heterocyclic ami nes, Particular attention is given to the predicted quantum chemical p roperties of the parent amines and their metabolites. A number of chem ical properties have been found to correlate well with measured mutage nic potency, including log P, the energies of the frontier orbitals of the parent amines, and the thermodynamic stability of the nitrenium i on, possibly the ultimate DNA-binding species. These correlations are intriguing clues to the mutagenic activity of the aromatic amines; how ever, many factors still await final explanation, including the exact mechanisms of the metabolic enzymes, the identity(s) of the ultimate D NA-binding species, the reaction mechanism in the DNA-adduction, the r ole of sequence context in the covalent and non-covalent binding of th e adducts, and the role of DNA repair. (C) 1998 Elsevier Science B.V. All rights reserved.