The substrate specificity of the rat hepatic cytosolic arylamine oxidase catalyzing the bioactivation of aromatic amines

Abstract

The ability of the cytosolic arylamine oxidase to convert structurally diverse aromatic and heterocyclic amines to mutagens in the Ames test was investigated using hepatic cytosol from Aroclor 1254-treated rats as the activation system. Using this system, only amino compounds containing at least three fused aromatic rings elicited a strong mutagenic effect; heterocyclic amines failed to exhibit mutagenicity. In contrast, when Aroclor 1254-induced rat hepatic microsomal preparations served as the activation system, monocyclic, bicyclic as well as larger amino compounds induced a clear mutagenic response; moreover, heterocyclic amines were potent mutagens. Nitrosamines displayed mutagenicity in the presence of only the microsomal activation system. In the presence of the cytosol, the mutagenic response of aromatic amines was much lower in the bacterial strain TA98-1,8-DNP 6, which is deficient in O-acetyltransferase activity, compared to the normal TA98 strain. This finding implies that the cytosolic activation of aromatic amines involves N-hydroxylation.