Inhibition by dietary menhaden oil of cyclooxygenase-1 and 2 in N-nitrosomethylurea-induced rat mammary tumors

Studies in laboratory animals and epidemiological surveys suggest a relatio nship between the type and amount of dietary fat and mammary cancer. One me chanism proposed to explain this relationship is modulation by dietary fat, of mammary tumor eicosanoid levels through action at the rate limiting enz yme in eicosanoid synthesis, cyclooxygenase (COX). Until recently there hav e been no studies which have examined COX gene expression in human breast o r rodent mammary tissues. In this study we have demonstrated the presence o f two immunoreactive isoforms of cyclooxygenase (COX-1 and -2), and the mod ulating effects of n-3 fatty acids on their expression, in N-nitrosomethylu rea (NMU)-induced rat mammary tumors. Three different high fat diets were c ompared namely, corn oil (CO) 23%; CO 18% menhaden oil (MO) 5%; CO, 5%/MO 1 8%; low fat corn oil (5%) served as a control. It was found that immunoreac tive COX-2 protein levels were approximately 3x higher than COX-1 levels in NMU-induced mammary tumors. Moreover, the high menhaden oil diet (rich in n-3 fatty acids) significantly suppressed both COX-1 (-28%) and COX-2 (-36% ) protein levels when compared to the high corn oil diet. No differences we re found among the other treatment groups when compared pair-wise or with l ow-fat control. The mechanism(s) by which n-3 fatty acids suppress COX-1 an d COX-2 remain to be determined.