Inhibition of benzo[a]pyrene-induced forestomach neoplasia in mice by citrus limonoids.

The limonoids, limonin and nomilin, are bitter principles found in common edible citrus fruits. Nomilin, when given three times (at 5 and 10 mg per animal) every two days, induced increased glutathione S-transferase activity 2.48 and 3.44 times over the control, respectively, in the liver of female ICR/Ha mice. The increases of GST activity in the small intestinal mucosa were 3.00 and 4.17, respectively, over the control. Limonin, when given at the same dose levels, was not active in the liver. However, marginal activity was obtained in the small intestinal mucosa. Nomilin, which is the more active enzyme inducer, was found to inhibit benzo[a]pyrene (BP)-induced neoplasia in the forestomach of ICR/Ha mice. The number of mice with tumors was reduced from 100 to 72%, and the number of tumors per mouse was significantly decreased as a result of nomilin treatment. Limonin, which is a weak enzyme inducer, was less potent as an inhibitor of BP-induced neoplasia. These findings suggest limonoids as a class of regularly consumed natural products may be effective chemopreventive agents.