Plant activation of aromatic amines mediated by cytochromes P450 and flavin-containing monooxygenases

To know the mechanisms involved in the activation of promutagenic aromatic amines mediated by plants, we used Persea americana S117 system (S117) for the activation of 2-aminofluorene (2-AF) and m-phenylenediamine (m-PDA) in Ames assays. In these assays, the effect of the diphenylene iodonium (DPI), an inhibitor of flavin-containing monooxygenases (FMOs), of the 1-aminoben zotriazole (I-ABT), an inhibitor of cytochromes P450 (cyt-P450s) and of the methimazole, a high-affinity substrate for FMOs, was studied. The efficacy of both inhibitors and of the methimazole was verified to find that they d id partially inhibit the mutagenesis of both aromatic amines, activated wit h rat liver S9. Similarly, both inhibitors and methimazole did produce a si gnificant decrease in 2-AF and m-PDA mutagenesis, when the activation syste m was S117, indicating that, similar to what occurs in mammalian systems, p lant FMOs and cyt-P450s can metabolize aromatic amines to mutagenic product (s). However, the affinity of both FMOs and cyt-P450s of plant for 2-AF and m-PDA was different. Data obtained indicate that the activities of plant F MOs must be the main enzymatic system of m-PDA activation while, in 2-AF ac tivation, plant cyt-P450s have the most relevant activities. In addition, p eroxidases of the S117 system must contribute to 2-AF activation and some i soforms of FMOs and/or cyt-P450s of the S117 system, uninhibited by the inh ibitors used, must be the responsible for a partial activation of m-PDA. (C ) 2000 Elsevier Science B.V. All rights reserved.