Inhibition of conjugated fatty acids derived from safflower or perilla oil of induction and development of mammary tumors in rats induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

Chemopreventive effects of conjugated fatty acids derived from safflower oil (CFA-S), which contains large amounts of conjugated linoleic acid, and from perilla oil (CFA-P) with abundant conjugated alpha-linolenic acid were examined in a 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced rat mammary carcinogenesis model. Groups of 20-22 6-week-old female Sprague-Dawley (SD) rats were given eight intragastric injections of PhIP at a dose of 100 mg/kg b.w. during the initial 8 week period. Powdered basal diets containing 0.1% CFA-S or CFA-P were applied during or after PhIP treatment until week 40. In the rats receiving CFA-S or CFA-P together with PhIP treatment, retardation of mammary tumor emergence was observed until week 27. The groups given CFA-S or CFA-P after PhIP treatment, in contrast, demonstrated significant decrease in the final incidences of mammary adenocarcinomas. The indices of proliferating cell nuclear antigen positive cells in mammary adenocarcinomas were significantly reduced with both CFA-S and CFA-P in the post-initiation phase. Formation of aberrant crypt foci in the colon and basophilic foci of the pancreas due to the PhIP treatment group were not affected by CFA-S or CFA-P. In a second short-term experiment, female SD rats were maintained on powdered basal diet containing 0.03% PhIP alone or together with 0.1% CFA-S or CFA-P for 4 weeks. Immunohistochemically, CFA-S and CFA-P were revealed to suppress PhIP-DNA adduct formation in the epithelial cells of mammary gland (duct and alveolar cells), colon and pancreas. These results indicated that CFA-P and CFA-S may retard development of PhIP-induced mammary tumors with inhibition of PhIP-DNA adduct formation, and decreased mammary carcinogenesis in the post-initiation period with inhibition of cell proliferation.