Price R J, Walters D G, Hoff C, Mistry H, Renwick A B, Wield P T, Beamand J A, Lake B G
BIBRA International, Carshalton, Surrey, UK.
Food Chem Toxicol. 1996 Jul;34(7):603-9. doi: 10.1016/0278-6915(96)00026-9.
Agaritine [(beta-N-[gamma-L(+)glutamyl]-4-hydroxymethylphenylhydrazine] is present in the common cultivated mushroom Agaricus bisporus and several agaritine derivatives have been shown to produce tumours in experimental animals. In this investigation the metabolism of [ring-U-14C]agaritine has been studied in precision-cut rat, mouse and human liver slices and in precision-cut rat and mouse lung slices. To confirm the functional viability of the tissue slice preparations, the metabolism of 7-ethoxycoumarin was also studied. Liver and lung slices from all species metabolized 50 microM 7-ethoxycoumarin to 7-hydroxycoumarin, which was conjugated with D-glucuronic acid and sulfate. Incubation of rat, mouse and human liver slices, and rat and mouse lung slices with 25 microM [14C]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 liver slices and was greater in mouse lung than in rat lung slices. No correlation was observed between agaritine metabolite covalent binding and tissue slice gamma-glutamyltransferase activity. Additional studies with mouse liver slices showed that [14C]agaritine was also metabolized to a number of unknown polar metabolites. These results demonstrate that agaritine can be metabolized by enzymes present in mammalian liver and lung.
伞菌氨酸[（β-N-[γ-L(+)谷氨酰基]-4-羟甲基苯肼）存在于常见的栽培蘑菇双孢蘑菇中，并且已经表明几种伞菌氨酸衍生物在实验动物中会引发肿瘤。在本研究中，已对[环-U-14C]伞菌氨酸在精确切割的大鼠、小鼠和人肝脏切片以及精确切割的大鼠和小鼠肺切片中的代谢情况进行了研究。为了确认组织切片制剂的功能活性，还研究了7-乙氧基香豆素的代谢情况。所有物种的肝脏和肺切片都将50微摩尔的7-乙氧基香豆素代谢为7-羟基香豆素，后者与D-葡萄糖醛酸和硫酸盐结合。用25微摩尔的[14C]伞菌氨酸孵育大鼠、小鼠和人肝脏切片以及大鼠和小鼠肺切片，会导致代谢产物随时间形成，这些代谢产物与组织切片蛋白共价结合。伞菌氨酸代谢产物的共价结合在小鼠肝脏中比在大鼠和人肝脏切片中更强，在小鼠肺中比在大鼠肺切片中更强。未观察到伞菌氨酸代谢产物共价结合与组织切片γ-谷氨酰转移酶活性之间的相关性。对小鼠肝脏切片的进一步研究表明，[14C]伞菌氨酸还会代谢为多种未知的极性代谢产物。这些结果表明，伞菌氨酸可被哺乳动物肝脏和肺中存在的酶代谢。
