Bioactivation of 6-aminochrysene by animal and human hepatic preparations: contributions of microsomal and cytosolic enzyme systems

Abstract

6-Aminochrysene was converted into mutagen(s), in the Ames test in the presence of Aroclor 1254-induced hepatic S9, microsomal and cytosolic fractions, the first being the least and the last the most efficient activation system. The cytosolic activation of 6-aminochrysene decreased in the presence of increasing amounts of microsomes. The Aroclor 1254-induced rat microsomal and cytosolic systems differed markedly in a number of properties, including their cofactor requirements and responses to prototype inducers of the cytochrome P450-dependent mixed-function oxidase system. The cytosolic activation system could also convert 2-aminochrysene to mutagens but not 2- and 6-methylchrysene. Human hepatic cytosol could convert 6-aminochrysene and 2-aminoanthracene to mutagens in the Ames test. It is concluded that a hepatic cytosolic oxygenase exists, totally different from the microsomal oxygenases, which metabolizes aminopolycyclic aromatic hydrocarbons to mutagens, presumably through N-oxidation. This oxygenase activity appears to be present in human hepatic cytosol.