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

• Published in: Mutation research Vol. 470; no. 2; pp. 155 - 160
• Main Authors: Chiapella, Carles, Radovan, Rodrigo D, Moreno, José Antonio, Casares, Lorena, Barbé, Jordi, Llagostera, Montserrat
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 31-10-2000; Elsevier
• Subjects: 2-Aminofluorene; Amines - pharmacokinetics; aromatic amines; Biological and medical sciences; Biotransformation; Chemical mutagenesis; Cytochrome P-450 Enzyme System - metabolism; cytochrome P450; Cytochromes P450; flavin; Flavin-containing monooxygenases; m-Phenylenediamine; Medical sciences; Mixed-function oxidases; monooxygenase; Mutagenicity Tests; Mutagens - pharmacokinetics; Oxygenases - metabolism; Persea americana; phenylenediamine; Plant activation; Toxicology; m-Phenylenediamine; Flavin-containing monooxygenases; 2-Aminofluorene; Plant activation; Mixed-function oxidases; Cytochromes P450; Thiamazole; Flavin enzyme; Enzyme; Mutagenicity testing; Toxicity; Cytochrome P450; Mixed function enzyme; Persea americana; Polycyclic aromatic compound; Salmonella typhimurium; Phenylenediamine; Peroxidases; Ames test; Dicotyledones; Angiospermae; Metabolic activation; Bacteria; Spermatophyta; Oxidoreductases; Lauraceae; Enterobacteriaceae
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/S1383-5718(00)00098-X

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-aminobenzotriazole (1-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 did partially inhibit the mutagenesis of both aromatic amines, activated with rat liver S9. Similarly, both inhibitors and methimazole did produce a significant decrease in 2-AF and
m-PDA mutagenesis, when the activation system was S117, indicating that, similar to what occurs in mammalian systems, plant 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 FMOs must be the main enzymatic system of
m-PDA activation while, in 2-AF activation, plant cyt-P450s have the most relevant activities. In addition, peroxidases of the S117 system must contribute to 2-AF activation and some isoforms of FMOs and/or cyt-P450s of the S117 system, uninhibited by the inhibitors used, must be the responsible for a partial activation of
m-PDA.