The mutagenic activity of agaritine — a constituent of the cultivated mushroomAgaricus bisporus —and its derivatives detected with the Salmonella/mammalian microsome assay (Ames Test)

ZusammenfassungGereinigtes Agaritin [N′-(γ-L(+)glutamyl)-p-hydroxymethylphenylhydrazin]; (ein im ZuchtchampignonAgaricus bisporus vorkommender Inhaltsstoff),p-Hydrazinobenzoesaure (eine hypothetische Vorstufe von Agaritin) sowie einige Abbauprodukte von Agaritin wurden mit Hilfe desSalmonella/Säuger-Mikrosomen-Tests (Ames Test) auf mutagene Aktivität untersucht. In Übereinstimmung mit Literaturdaten zeigte Agaritin eine deutliche direkt wirkende mutagene Aktivitat mitSalmonella typhimurium TA1537 (30 Revertanten/gmol) and TA97. Inkubation von Agaritin bei alkalischem pH führte zu einem pH-abhangigen Anstieg der Mutagenität. Inkubation von Agaritin mitγ-Glutamyltransferase (GT) während 10 h (Zimmertemperatur; pH 8.2) führte sogar zu einer 8- bis 16 fachen Zunahme der Mutagenität. Synthetischesp-Hydroxymethylphenylhydrazin (das vermutliche Produkt des durch die GT katalysierten Abbaus von Agaritin) zeigte allerdings eine nur etwa 3- bis 6 mal höhere mutagene Aktivität als Agaritin. Das hypothetische ultimate Mutagen, das Hydroxymethyldiazonium-Ion, welches auch inA. bisporus vorkommt, zeigte die höchste Mutagenität (TA1537: ca. 300 bis 1000 Revertanten/gmol).SummaryPurified agaritine (N′-(γ-L(+)-glutamyl)-p-hydroxymethylphenylhydrazine) isolated fromAgaricus bisporus,p-hydrazinobenzoic acid (its presumptive precursor) and some agaritine-degradation products were tested for mutagenic activity with theSalmonella/mammalian microsome assay (Ames test). Consistent with the literature, agaritine showed a distinct direct-acting mutagenicity with the strain TA1537 (30 revertants/gmol) and with TA97. Incubation of agaritine at alkaline pH increased the mutagenic effect. Pre-incubation of agaritine with γ-glutamyl transferase (GT) during 10 h at room temperature (pH 8.2) even enhanced the mutagenicity by a factor of 8 to 16 depending on the strain. In accordance with this finding, syntheticp-hydroxymethylphenylhydrazine (the presumptive product of the GT catalyzed degradation) showed also a distinct direct-acting mutagenicity, but the increase was only about 3- to 6-times compared with agaritine. The hypothetical ultimate mutagenic metabolite of agaritine, thep-hydroxymethylbenzenediazonium ion, a compound occuring naturally inA. bisporus, showed the highest mutagenic activity (with TA1537 approximately 300 to 1000 revertants/μol).

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