Mutagenicity of high fat diets in the colon and small intestine of transgenic mice.

Dietary fat has been implicated as a cause of colon cancer by epidemiological studies. Unfortunately, these studies are compatible with high fat as either initiator or promoter. Since initiators are normally mutagenic, we have tested the mutagenicity of high fat diets in the intestinal epithelium at two loci. The Dlb-1 assay, used in the small intestine, detects a wide spectrum of mutations. The lacI assay (Big Blue Mouse assay) is not as sensitive to some types of mutation as is Dlb-1 but was used in the colonic epithelium. Mice suitable for both assays were fed isocaloric high fat diets and subsequently assayed for somatic mutation. The diets consisted of: (i) a mixture of beef tallow, butter and lard totalling to 31% w/w of the diet (AIN-76A) up to 17 weeks; and (ii) corn oil, beef tallow, lard or butter individually, at 31% w/w of the diet for 5 and 9 weeks. These diets provided 50% of the calories from fat. The weights of the experimental and control mice were similar throughout the experiment. No significant increases in mutant frequencies were observed on any high fat diet compared to controls, so we conclude that uncooked fats are not mutagenic and are not initiators of carcinogenesis in the intestinal epithelium.