The essential fatty acid requirement for azoxymethane-induced intestinal carcinogenesis in rats

The essential fatty acid requirement for the development of intestinal carcinogenesis was determined and compared to the overall essential fatty acid status of the animals as measured by the triene/tetraene ratio in the plasma, liver and colon. To induce tumors, male Sprague-Dawley rats were given two weekly injections (20 mg/kg body wt) of azoxymethane. Two weeks after the last injection, the rats were divided into groups of 25 and given one of six diets containing various levels of essential fatty acids (as linoleate). The diets contained 5% total fat and were prepared by mixing safflower oil (high essential fatty acids, beef fat (low essential fatty acids), and medium chain triglyceride oil (no essential fatty acids). One group of rats was fed a 20% beef fat diet. The range of essential fatty acids was from <0.03% to 1.28% (w/w). Twenty-six weeks after the first azoxymethane injection, the animals were killed and intestinal tumor incidence and multiplicty were determined. Samples of plasma, liver and colon were also taken for measurement of the triene/tetraene ratio by gas chromatography. Large bowel tumor incidence showed a dependence on the essential fatty acid content of the diet. The results were as follows: (percent essential fatty acids: percent tumor incidence) Group A (1.28∶ 72.4), Group B (0.60∶ 73.3), Group C (0.11∶ 55.2), Group D (0.08∶ 39.3), Group E (<0.03∶ 37.9) and Group F, which was fed 20% beef fat, (0.34∶ 88.5). These data suggest the essential fatty acid requirement for colon tumorigenesis is much lower than values previously reported for tumorigenesis in the breast and pancreas. The plasma and liver triene/tetraene ratios showed clear-cut essential fatty acid deficiency (ratio >0.4) in Groups D and E, although no clinical symptoms were evident. In all dietary groups, the triene/tetraene ratio in the colon was lower than 0.3. In addition in the colon, the percentage of fatty acids present as 20 carbon polyunsaturated fatty acids was lower than in the plasma and liver. These data suggest the colon possesses low levels of the fatty acid desaturase and elongase needed for conversion of linoleate to 20 carbon fatty acids, and therefore, that the colonic requirement for essential fatty acids may be low. Furthermore, in the absence of other clinical symptoms, the reduced tumorigenesis observed in the groups fed low essential fatty acids suggests the essential fatty acid requirement of tumor tissue may be higher than that of normal colon mucosa.