The role of dietary long-chain n-3 fatty acids in anti-cancer immune defense and R3230AC mammary tumor growth in rats: Influence of diet fat composition

We determined if long-chain n-3 fatty acids fed as part of a: (1) high polyunsaturated fat diet (currently recommended by several health agencies) or (2) low polyunsaturated fat diet (representative of that consumed by a large segment of the North American population) improved antitumor immune defense and inhibited tumor growth. Rats were fed one of four semi-purified diets (20% w/w fat) for 21 days pre- and 17 days post- R3230AC mammary tumor implantation. The polyunsaturated to saturated fatty acid (P/S) ratio was either 1 (high P/S diet) or 0.35 (low P/S diet). At each P/S ratio, diets provided long-chain n-3 fatty acids at 0 or 5% w/w of total fat. Long-chain n-3 fatty acids fed in a high P/S diet did not affect tumor growth or host immune responses. In contrast, feeding long-chain n-3 fatty acids in a low P/S diet increased natural killer cell cytotoxicity, splenocyte nitric oxide and interleukin-2 production, and the proportion of activated (CD25(+)) CD8(+) and CD28(+) cells, but did not significantly inhibit tumor growth. For both P/S diets, tumor cells from rats fed long-chain n-3 fatty acids had a higher n-3 content and n-3/n-6 ratio in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Furthermore, the magnitude of increase in n-3 fatty acid incorporation into tumor phospholipids was greater when fed in a low P/S diet. We demonstrated that the dietary P/S ratio significantly influences the effect of long-chain n-3 fatty acids on host immune responses and n-3 fatty acid incorporation into tumor cells. These findings warrant further consideration when designing dietary recommendations.