Effect of vegetable and carotenoid consumption on aberrant crypt multiplicity, a surrogate end-point marker for colorectal cancer in azoxymethane-induced rats

Epidemiological studies indicate that increased vegetable consumption reduc es the risk of colorectal cancer mortality. In the present study we have in vestigated the effect of consumption of standard diets supplemented with fr eeze-dried vegetables (peas, spinach, sprouts and broccoli) and carotenoids (all-trans beta-carotene and palm oil carotenoid extract) on surrogate end -point markers for colorectal cancer in an azoxymethane-induced rat model. Mean aberrant crypt multiplicity was reduced (19%) by the pea-supplemented diet only (P < 0.05), The vegetable-induced effect was more apparent in abe rrant crypt foci with higher multiplicity. Intervention with diets suppleme nted with peas, spinach, sprouts and a mix of all vegetables reduced the nu mber of foci with >2 aberrant crypts/focus by 37, 26, 23 and 26%, respectiv ely (P < 0.05), Even more pronounced effects were observed in foci with >3 aberrant crypts/focus, with reductions of similar to 50% in the pea and spi nach intervention groups. All-trans beta-carotene and palm oil-derived caro tenoids, supplied at similar doses to those expected in the vegetable diets , inhibited ACM only marginally. Aberrant crypt foci formation in groups fe d a sprout-supplemented diet prior to or following azoxymethane treatment w as similar, indicating that this effect is due to inhibition of promotion r ather than initiation of colorectal carcinogenesis. Vegetable and carotenoi d consumption did not affect in situ proliferation of colonic crypt cells, as assessed by semi-automated image analysis of bromodeoxyuridine (BrdU)-po sitive nuclei. BrdU-negative nuclei of colonic crypt cells were reduced sli ghtly in the combined vegetable groups, as compared with the control (P < 0 .05), These data: (i) are in line with epidemiological evidence regarding b eneficial effects of vegetable consumption on colorectal carcinogenesis; (i i) indicate that consumption of several types of vegetables inhibits early post-initiation events in colorectal carcinogenesis; (iii) suggest that the vegetable-induced effect is more pronounced in advanced lesions; (iv) indi cate that the carotenoid content of the vegetables (alpha- and beta-caroten e) contributes only marginally to the vegetable-induced effects.