2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a food-derived heterocyclic amine in cooked meat, was determined to be a mammary gland carcinogen in female Sprague-Dawley rats on a high fat diet. With our protocol, tumors are induced by a 10-dose regimen of PhIP after a short latency period (25 weeks after treatment). The mammary tumor incidence, growth rate, and invasiveness was shown to be affected by the level of dietary fat given to the rats. A high-fat diet (23.5% corn oil) resulted in approximately a threefold higher incidence of mammary gland cancer than a low fat diet (5% corn oil). Tumors were examined for H-ras codons 12 and 13 mutations by sequencing. H-ras mutation frequency was threefold lower in animals on a high fat diet than in animals on a low fat diet. In addition, only in tumors from animals on a low fat diet were both codons found to be mutated. Differential display was set up to further compare genetic alterations between tumors from animals on high and low fat. B-Casein and transferrin were shown to be differentially expressed in tumors from animals on high and low fat diets. Epithelial cell lines from rat mammary gland tumors are being derived for cytogenetic analysis. To date G-banding has revealed an apparent duplication of a portion of the long arm of chromosome 1.
