In the present study, we investigated the effects of high levels of dietary
fish oil on the growth of MX-1
human mammary carcinoma and its response to
mitomycin C (MC) treatment in athymic mice. We found that high levels of dietary
fish oil (20%
menhaden oil + 5%
corn oil, w/w) compared to a control diet (5%
corn oil, w/w) not only lowered the
tumor growth rate, but also increased the
tumor response to MC treatment. We also found that high levels of dietary
fish oil significantly increased the activities of
tumor xanthine oxidase and
DT-diaphorase, which are proposed to be involved in the bioreductive activation of MC. Since
menhaden oil is highly unsaturated, its intake caused a significant increase in the degree of
fatty acid unsaturation in
tumor membrane
phospholipids. This alteration in
tumor membrane
phospholipids made the
tumor more susceptible to oxidative stress, as indicated by the increased levels of both endogenous lipid peroxidation and
protein oxidation after feeding the host animals the
menhaden oil diet. In addition, the
tumor antioxidant enzyme activities,
catalase (CAT),
superoxide dismutase (SOD),
glutathione peroxidase (GPOx), and
glutathione S-transferase peroxidase (GSTPx), were all significantly enhanced by feeding a diet high in
fish oil. MC treatment caused further increases in
tumor lipid peroxidation and
protein oxidation, as well as in the activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative stress in this
tumor model which is exacerbated by feeding a diet high in
menhaden oil. Thus, feeding a diet rich in
menhaden oil decreased the growth of
human mammary carcinoma MX-1, increased its responsiveness to MC, and increased its susceptibility to endogenous and MC-induced oxidative stress, and increased the
tumor activities of two
enzymes proposed to be involved in the bioactivation of MC, that is,
DT-diaphorase and
xanthine oxidase. These findings support a role of these two
enzymes in the bioactivating of MC and indicate that the type of
dietary fat may be important in
tumor response to
therapy.