Synergistic suppression of azoxymethane-induced foci of colonic aberrant crypts by the combination of β-carotene and perilla oil in rats

The modulating effect of the combined dietary feeding of β-carotene and perilla oil, which is rich in α-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Rats received oral administration of β-carotene (0, 50 or 200 mg/kg body weight/day) and fed a basal diet containing either 12% olive oil, 3% perilla oil plus 9% olive oil, or 12% perilla oil. A dose-dependent suppressive effect of perilla oil was found. The numbers of ACF were 42.0 and 18.4% of those of the 12% olive oil-fed controls in the rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. The development of ACF was also reduced significantly by the addition of dietary β-carotene in each of the oil-fed groups (P < 0.05, respectively). The suppression by the combination of β-carotene and perilla oil was synergistic, as the numbers of ACF were 12.9 and 8.9% of those of the 12% olive oil-fed controls in β-carotene-treated rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. β-Carotene plus perilla oil also suppressed the numbers of silver-stained nucleolar organizer regions and the expression of ras mRNA in the colonic mucosa (cell proliferation biomarkers). Following administration of β-carotene, a significant increase in the concentration of intact β-carotene molecules was found in the colonic mucosa, livers, and sera. However, no accumulation of retinoids was observed in the colonic mucosa, suggesting that the inhibitory effect may not be related to the provitamin A activity. These results suggest that the combination of β-carotene and perilla oil may be useful in the prevention of colon cancer.