text: OBJECTIVE: The effects of different dietary oils on the development of colitis-associated colon cancer have not been studied. The present study examined the effect of different dietary oils on the severity of chronic colitis, development of colitis-associated premalignant changes, and colonic expression of cyclooxygenase-2 (COX-2) in interleukin-10 knockout (IL-10-/-) mice. METHODS: IL-10-/- mice were fed chow supplemented with corn oil (CO; control, n=28), olive oil (OO; n=29), or fish oil (FO; n=35) for 12 wk and their colons were studied for colitis score, premalignant changes, and COX-2 expression. RESULTS: The average colitis score was higher in the FO than in the CO group. Similarly, the incidence of severe colitis (score>or=3) was significantly higher in the FO than in the CO and OO groups (50% versus 7.7% and 3.7%, respectively, P<0.05). Dysplasia was more frequent in the FO and less frequent in the OO than in the CO group (47% and 4% versus 15%, respectively, P<0.05). Conversely, aberrant crypt foci and crypt index were significantly higher in the FO than in the CO group. Colitis score, aberrant crypt foci, and crypt index did not differ between the OO and CO groups. COX-2 immunostaining was significantly lower in the OO than in CO group (P<0.05) but not different between the FO and CO groups. CONCLUSIONS: In IL-10-/- mice, fish oil exacerbates chronic colitis and colitis-associated premalignant changes. Conversely, olive oil inhibits COX-2 immunostaining and decreases the risk of neoplasia associated with chronic colitis.