METABOLISM OF [RING-U-C-14] AGARITINE BY PRECISION-CUT RAT, MOUSE ANDHUMAN LIVER AND LUNG SLICES

Agaritine amma-L(+)glutamyl]-4-hydroxymethylphenylhydrazine} is presen t in the common cultivated mushroom Agaricus bisporus and several agar itine derivatives have been shown to produce tumours in experimental a nimals. In this investigation the metabolism of [ring-U-C-14]agaritine has been studied in precision-cut rat, mouse and human liver slices a nd in precision-cut rat and mouse lung slices. To confirm the function al viability of the tissue slice preparations, the metabolism of 7-eth oxycoumarin was also studied. Liver and lung slices from all species m etabolized 50 mu M 7-ethoxycoumarin to 7-hydroxycoumarin, which was co njugated with D-glucuronic acid and sulfate. Incubation of rat, mouse and human liver slices, and rat and mouse lung slices with 25 mu M [C- 14]agaritine resulted in a time-dependent formation of metabolite(s), which bound covalently to tissue slice proteins. Agaritine metabolite covalent binding was greater in mouse liver than in rat and human live r slices and was greater in mouse lung than in rat lung slices. No cor relation was observed between agaritine metabolite covalent binding an d tissue slice gamma-glutamyltransferase activity. Additional studies with mouse liver slices showed that [C-14]agaritine was also metaboliz ed to a number of unknown polar metabolites. These results demonstrate that agaritine can be metabolized by enzymes present in mammalian liv er and lung. Crown copyright (C) 1996 Published by Elsevier Science Lt d.