Abstract
A223
Polyunsaturated fatty acid metabolites are known to be involved in inflammation, and fatty acid precursors and metabolites may also exert genomic control over the expression of genes involved in proliferation and differentiation. Some researchers suggest that a higher ratio of omega-3/omega-6 fatty acids would be beneficial in cancer prevention and therapy, either alone or as an adjuvant to traditional treatments. In this study, we examined whether dietary supplementation with fish oil (with a high omega-3/omego-6 ratio) or corn oil (with a low omega-3/omega-6 ratio) could influence lung carcinogenesis in the NNK carcinogen-induced mouse model of lung cancer. A/J mice (n=14/group) were fed AIN-93M semi-purified rodent diet alone or supplemented with menhaden fish oil (10% wt/wt), corn oil (10% wt/wt), or soybean oil (10% wt/wt, as an isocaloric control) for three weeks prior to a single dose carcinogen injection (100 mg NNK/kg body weight), and 17 weeks thereafter. We found that dietary supplementation with 10% menhaden fish oil was able to decrease lung tumor multiplicity by 78%, compared to a control group receiving soybean oil supplementation (80% decrease vs. NNK injection alone). Corn oil supplementation had no effect on tumor incidence or tumor multiplicity. The mechanism behind these chemopreventive effects remains elusive, but does not seem to involve modulation of the nuclear hormone receptors RXRα, RARβ, or PPARγ; the cyclin dependent kinase inhibitor p21; the inducible enzyme cyclooxygenase-2; nor modulation of the mitogen IGF-I or its binding protein IGFBP-3 in total lung tissue. Ongoing research aims to determine molecular changes occurring at tumor initiation sites and molecular mechanisms of action at the cellular level.
[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]