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 cry pt foci (ACF) was investigated in male F344 rats. The effects of d-lim onene intake on ornithine decarboxylase (ODC) activity and on the silv er stained nucleolar organizer region protein (AgNOR) count in the col onic mucosa were also estimated, Animals were given 3 weekly s.c. inje ctions of AOM (15 mg/kg body wt) to induce ACF. These rats were treate d with or without 0.5% d-limonene in the drinking water, starting 1 we ek before the first dosing with AOM. All rats were killed 2 weeks afte r the last AOM injection, to measure the number of ACF, ODC activity a nd 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 A OM alone (P < 0.01, P < 0.001 and P < 0.001 respectively). Number of A gNOR counts/nucleus of rats treated with AOM and d-limonene was signif icantly smaller than that of rats treated with AOM alone (P < 0,001). These results suggest that the monoterpenoid d-limonene might be a che mopreventive agent for colonic carcinogenesis in rats.