Lymphocyte Activation, T-Cell Cytotoxicity and Their Relationship to Dietary Fat Enhanced Murine Mammary Tumorigenesis

155 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1986.It has been well established that raising dietary fat increases the incidence of breast tumors in rodents. It has also been postulated that higher levels of dietary fat increase tumorigenesis by lowering immune function. The objectives of this research were to examine the effects of dietary soybean oil (SBO) concentration (5 vs. 20% by weight) on mammary tumorigenesis, mitogen-induced lymphocyte blastogenesis, cell-mediated cytotoxicity, and serum and lymphocyte fatty acid composition in C3H/OUJ female mice. Weanling mice fed 20% SBO for nine months had a higher incidence (89 vs. 65%) and greater average size (2.9 vs. 1.9 g) of mammary tumor virus type S positive breast tumors than mice fed 5% SBO. The response of isolated splenocytes to the T-cell mitogens, concanavalin A and phytohemagglutinin was 20%-25% lower in mice fed 20% SBO compared to mice fed 5% SBO after twenty weeks of feeding. There was no effect of SBO concentration on the splenocyte response to the B-cell mitogen, lipopolysaccharide or to the B- and T-cell mitogen, pokeweed mitogen. The effects of raising dietary SBO on the kinetics of T-cell cytotoxicity were examined and the two parameters, K(, 1/2) and V(,max) were calculated from the experimental data. There was no influence of dietary SBO on the K(, 1/2), indicating that binding of the T-killer cells to their target cells was similar for both treatments. Splenocytes from mice fed 20% SBO had a significantly lower V(,max) than splenocytes from mice fed 5% SBO. The reduction in maximum velocity as dietary SBO was raised may reflect a reduced clonal expansion of T-killer cells following immunization, a reduced lytic efficiency due to fewer receptors, or a lower capacity to deliver the lethal hit. The lower cell-mediated immunity associated with 20% SBO, was not due to changes in the fatty acid composition of the two major splenocyte membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine. However, serum levels of linoleic acid were higher in mice fed 20% SBO. In conclusion, the capacity of splenocytes to kill allogeneic tumor cells was lowered with levels of dietary soybean oil, which increased the incidence and size of breast tumors in the same animal model. The lipid metabolite(s) and mechanism(s) responsible are not known. The development of immune assays against specific tumor antigens is expected and will greatly assist elucidating the role of the immune system in dietary fat enhanced breast cancer.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD