The mutagenic activity of agaritine--a constituent of the cultivated mushroom Agaricus bisporus--and its derivatives detected with the Salmonella/mammalian microsome assay (Ames Test).
Purified agaritine (N'-(gamma-L(+)-glutamyl)-p-hydroxymethylphenylhydrazine) isolated from Agaricus bisporus, p-hydrazinobenzoic acid (its presumptive precursor) and some agaritine-degradation products were tested for mutagenic activity with the Salmonella/mammalian microsome assay (Ames test). Consistent with the literature, agaritine showed a distinct direct-acting mutagenicity with the strain TA1537 (30 revertants/mumol) and with TA97. Incubation of agaritine at alkaline pH increased the mutagenic effect. Pre-incubation of agaritine with gamma-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, synthetic p-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, the p-hydroxymethylbenzenediazonium ion, a compound occurring naturally in A. bisporus, showed the highest mutagenic activity (with TA1537 approximately 300 to 1,000 revertants/mumol).
D000363:Agaricales / Q000378:metabolism*; D000364:Agaricus / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D006863:Hydrogen-Ion Concentration; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism; D010659:Phenylhydrazines / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D009153:Mutagens; D010659:Phenylhydrazines; D005723:gamma-Glutamyltransferase; C015654:agaritine