Diverse effect of fish oil on the growth of aberrant crypt foci and tumor multiplicity in F344 rats

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Abstract
The main objective of the present study was to investigate the amenability of preneoplastic lesions at different developmental stages to the growth‐regulatory effects of two types of dietary lipids. F344 male rats were given three injections of azoxymethane (15 mg/kg) and fed a low‐fat corn oil diet for 12 weeks to allow preneoplastic lesions or aberrant crypt foci (ACF) to develop. At this time, the colons of rats had a large number of ACF exhibiting various crypt multiplicities (number of crypts/focus). These rats were then randomly allocated to three dietary groups: high‐fat corn oil (HFC), high‐fat fish oil (HFF), and low‐fat corn oil (LFC). The number and crypt multiplicity of ACF and adenomatous lesions were determined after 6 and 12 weeks of dietary intervention. After six weeks, the HFF group had the highest number of ACF of all crypt multiplicities and microadenomas among the dietary groups. After 12 weeks of feeding, the HFC diet increased the number of tumors without significantly changing the number of ACF. In contrast, the HFF diet increased significantly (p < 0.05) the number of ACF with higher crypt multiplicity without affecting the number of tumors. Consequently, the total number of tumors per group in decreasing order was as follows: HFC > LFC > HFF. These findings suggest that dietary lipids varying in fatty acid composition, namely corn oil and fish oil, exerted a growth‐enhancing and ‐inhibiting effect, respectively, on different preneoplastic stages in a selective and differential manner. Most notably, transition of microscopic preneoplastic lesions to macroscopic lesions (microadenomas or adenomas) appears to be retarded by an HFF diet.