The induction of intestinal neoplasms in rats with the glycoside cycasin and its aglycone.

Abstract

Experiments are described dealing with the carcinogenic effects of (1) the crude cycad seed material, (2) the glycoside, cycasin, aβ-D-glucosyloxyazoxymethane, isolated from the crude material, and (3) the first metabolic breakdown product of cycasin, the aglycone of cycasin or methylazoxymethanol, on the intestinal tract of rats. While the crude material and cycasin produced tumors exclusively located in the large intestine, the aglycone when injected intraperitoneally, resulted in neoplasms of the small intestine as well. Supportive experiments in germfree animals are cited which indicate that cycasinper se, whether present in the intestinal tract or absorbed and excreted, is innocuous. Apparently, the glycoside is converted in conventional rats into the highly toxic aglycone through aβ-glucosidase of bacterial origin. Hence, it would seem likely that the carcinogenicity of the crude cycad material and of cycasin depends on a bacterial flora capable of providing the enzyme necessary for the liberation of the aglycone.