Aromatic amine carcinogenesis: Activation and interaction with nucleic acid bases

Abstract

Aromatic amines are indirectly acting carcinogens requiring multiple metabolic transformation to hydroxylamines and their ultimate active form. Current evidence implicates arylnitrenium ions as the ultimate carcinogen of this class of compounds. Using semiempirical molecular orbital methods, the electronic parameters related to metabolic activation and the stability and electro-philicity of these ultimate carcinogens were calculated for a series of aromatic amines. In addition, both semiempirical quantum mechanical perturbation and empirical potential methods have been used to characterize incipient covalent complexes of arylnitrenium ions with guanine and adenine. Such complexes could be intermediates in adduct formation at different base sites. The results of these studies are used to correlate to carcinogenic or mutagenic activity and to obtain insight into the specificity of adduct formation with DNA.