Bioactivation of 6-aminochrysene by animal and human hepatic preparations: contributions of microsomal and cytosolic enzyme systems.
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.
Marczylo
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Division of Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK.
Ioannides
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C
D000818:Animals; D001711:Biotransformation; D002911:Chrysenes / Q000493:pharmacokinetics* / Q000633:toxicity; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D005289:Ferrets; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013552:Swine
D002911:Chrysenes; D009153:Mutagens; C100101:6-chrysenamine