A classic example of the role of the intestinal flora in generating carcinogens is illustrated by the action of this bacterial enzyme on the plant derived compound cycasin (56). Cycasin is a naturally occurring beta-glucoside of methylazoxymethanol, extractable from the seeds and roots of cycad plants. It was observed that when Cycasin was fed to infant rats a number of different tumors developed. The Cycasin-induced tumors included hepatomas, renal sarcomas, squamous-cell carcinomas of the ear duct, and most frequently large bowel and duodenal adenocaricomas (56). The genetic strain of the rat did not appear to have a major influence on tumor development. It was, however, noted that the intestinal flora was required for tumorgenesis, since when Cycasin was given orally to germfree rats no tumors were observed (57). The discovery of the carcinogenicity of Cycasin led to experiments to test the precursor aglycones of Cycasin azoxymethane, azomethane, and dimethylhydrazine. These compounds were carcinogenic in conventional and germfree rats (58). The route of administration was not critical, and tumors developed after oral or subcutaneous administration (56). These results confirmed that the hydrolysis by the intestinal flora of the glycosidic bond was required for the activation of Cycasin. It was also observed that infant but not adult rats developed tumors when given Cycasin by intraperitoneal injection confirming the observation that tissue b-glucosidase disappeared in rats after 3 weeks of life (56).

Many other plant natural products occur as glycosides. These glycosides do not demonstrate mutagenicity when tested in the Salmonella test; however, upon hydrolysis of the glucosidic linkages they become mutagenic. There have been several studies showing mixed fecal cultures or fecal isolates of Streptococcus faecium can convert non-mutagenic rutin (quercetin-3-D-beta-D-glucose-alpha-L-rhamnose) to quercetin (59). Quercetin has been shown to be mutagenic in the Ames salmonella assay. Red wine and tea contain glycosides of quercetin.

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