Effects of dietary fish oil on human mammary carcinoma and on lipid-metabolizing enzymes

The growth rate of a human mammary carcinoma, MX‐1, was significantly reduced in athymic “nude” mice fed fish oil. Tumors from the fish oil‐fed animals also showed a greater sensitivity to two anti‐neoplastic agents, mitomycin C and doxorubicin. Mitochondria were isolated from control livers, host livers and tumors from fish oil‐and corn oil‐fed animals, and increased levels of 20∶5n−3 and 22∶6n−3 were found in mitochondrial lipids in all three tissues from the fish oil‐fed animals. To investigate the effect of dietary n−3 fatty acids on lipid metabolism, the activity of the acyl‐CoA:carnitine acyltransferase and three acyl‐CoA desaturases were measured. Carnitine acyltransferase activity toward all four acyl‐CoA substrates tested was markedly increased in mitochondria from liver by feeding fish oil. In mitochondria from tumors, feeding fish oil resulted in an increased activity toward only 18∶3n−3. These data suggest that fish oil may induce an increase in the oxidation of fatty acids. The Δ9‐desaturase activity was decreased in microsomes from liver and tumor from fish oil‐fed animals. However, both the Δ6 and Δ5 desaturases were increased in tumor and in control liver as a result of feeding fish oil. The Δ5 desaturase was not altered in microsomes from the host animals. The effect of fish oil on the Δ5 and Δ6 desaturases may involve alterations to metabolism of specific polyunsaturated fatty acids especially in the tumor tissue.