Tumor induction in germfree rats with methylazoxymethanol (MAM) and synthetic MAM acetate

The glucoside cycasin, an effective hepatotoxin and carcinogen in conventional rats, fails to produce these effects when administered to germfree rats. The hepatotoxic and carcinogenic effects of cycasin can also be elicited after prior hydrolysis to the aglycone. The aglycone (MAM) and the synthetic aglycone acetate ester produce all the effects in germfree rats of which the intact glucoside is capable only when fed to conventional rats. The aglycone is therefore the proximate carcinogen. Its liberation from the glucoside in conventional rats is mediated in the intestinal tract by a beta-glucosidase of bacterial origin. Intraperitoneal administration of the synthetic aglycone acetate and the free aglycone appears to be the most effective route for tumor induction and, of these resulting tumors, the most frequent are in the intestinal tract.