Fish oil enhances targeted apoptosis of colonocytes within the first 12 hours of carcinogen exposure and results in lower levels of DNA damage compared to corn oil.
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We have recently shown that fish oil protects against experimentally-induced colon cancer during the promotion phase primarily by enhancing apoptosis rather than decreasing cell proliferation. In this study we determined if fish oil is also protective by enhancing apoptosis during the initiation stage in response to DNA damage. Thirty male rats were provided with corn oil or fish oil, injected with azoxymethane, and terminated 0, 3, 6, 9 or 12 h later. Targeted apoptosis and DNA damage were assessed by cell position within the crypt using the TUNEL assay and quantitative immunohistochemical analysis of O6-methylguanine adducts, respectively. Most of the apoptosis was found toward the base of the crypt where the stem cells are located (41.74% in the bottom 1/3 of the crypt compared to 0.81% in the top 1/3, P<0.001). However, fish oil had the greatest effect on apoptosis at the top 1/3 of the crypt, doubling the apoptotic index compared to corn oil (P<0.01). There were lower levels of adducts throughout the 12 h time course of the study with fish oil vs corn oil (P<0.001). In the top 1/3 of the crypt, fish oil caused an incremental stimulation of apoptosis with increased adduct level, whereas, there was a negative regression between apoptosis and adduct incidence with corn oil feeding (P<0.03). Since polyps and tumors eventually develop from loss of growth control and retention of cells at the top of the crypt, the significant difference in fish oil vs corn oil on apoptosis targeted to this region may account, in part, for the observed protective effect of fish oil against experimentally-induced colon cancer.
