Wednesday, April 30, 2008

Fecalase: a model for activation of dietary glycosides to mutagens by intestinal flora

Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalian metabolism but does not provide a source of the enzymes present in intestinal bacterial flora that hydrolyze the wide variety of glycosides present in nature. We describe a stable cell-free extract of human feces, fecalase, which is shown to contain various glycosidases that allow the in vitro activation of many natural glycosides to mutagens in the Salmonella/liver homogenate test. Many beverages, such as red wine (but apparently not white wine) and tea, contain glycosides of the mutagne quercetin. Red wine, red grape juice, and tea were mutagenic in the test when fecalase was added, and red wine contained considerable direct mutagenic activity in the absence of fecalase. The implications of quercetin mutagenicity and carcinogenicity are discussed.

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