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Dietary fish oil down‐regulates pro‐inflammatory gene expression in colonocytes

Inflammatory bowel disease increases the risk of colon cancer development. The mechanisms behind this are based on the cellular consequences of oxidative stress. We have previously shown that dietary fish oil protects against inflammation‐induced oxidative DNA damage by upregulation of apoptosis. To determine the biological processes ultimately responsible for the protective effect of dietary fish oil on inflammation, we determined the transcriptional profile in colonocytes using CodeLink microarrays. Sprague Dawley rats were provided with corn or fish oil containing diets for 3 wk. Dietary fish oil increased glutathione S‐transferase (p= 0.007) expression, but decreased inflammation‐related gene RelA (NFkB, p65) (p=0.0001), NFkB (p105) (p=0.006) and RNY 18366 (p=0.0007) compared to the corn oil group. Fish oil‐fed rats had lower levels of CDP‐diacylglycerol synthase expression (p=0.005), which is a key enzyme in the regulation of PIP2, and p21‐activated kinase 2 and SH3 domain binding protein CR16, which are associated with MAP kinase signaling. The dietary fish oil group had greater bax expression (p=0.0009) compared to the corn oil group, which may contribute to the observed greater apoptosis in fish oil rats. In conclusion, dietary fish oil may protect against colon cancer by decreasing pro‐inflammatory genes involved in the NFkB‐, MAP kinase‐ and phosphoinositide‐mediated signaling pathways. This may account for the previously observed lower oxidative DNA damage level in fish oil‐fed rats and contribute towards one protective mechanism of fish oil against colon cancer.