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.