Inhibitory effects of d-limonene on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats.

The modifying effect of the monoterpenoid d-limonene in drinking water on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. The effects of d-limonene intake on ornithine decarboxylase (ODC) activity and on the silver stained nucleolar organizer region protein (AgNOR) count in the colonic mucosa were also estimated. Animals were given 3 weeks s.c. injections of AOM (15 mg/kg body wt) to induce ACF. These rats were treated with or without 0.5% d-limonene in the drinking water, starting 1 week before the first dosing with AOM. All rats were killed 2 weeks after the last AOM injection, to measure the number of ACF, ODC activity and AgNOR count/nucleus in the colon. In rats given AOM and d-limonene the frequencies of ACF and aberrant crypts/colon, and aberrant crypts/focus were significantly decreased compared with those of rats given AOM alone (P < 0.01, P < 0.001 and P < 0.001 respectively). Number of AgNOR counts/nucleus of rats treated with AOM and d-limonene was significantly smaller than that of rats treated with AOM alone (P < 0.001). These results suggest that the monoterpenoid d-limonene might be a chemopreventive agent for colonic carcinogenesis in rats.