ORTH, ME*; MONCURE, KG; WILLIAMS, EE; Salisbury University; Salisbury University; Salisbury University: The comparative effects of DHA on T27A murine leukemia cells and CHSE and ZFL fish cells

Docosahexaenoic acid (DHA) is the longest and most unsaturated of the omega 3 fatty acids commonly found in cell membranes. As a component of cell membranes, it appears to play an important, but unidentified role in the health of poikilotherms. Yet, elevated proportions of DHA in the membranes of tumor cells can cause tumor cell death. We are interested in understanding these contradictory effects of DHA. Earlier, we found that DHA induces apoptosis rather than necrosis in murine leukemia cells (T27A cells). The main enzymes involved in triggering apoptosis are the caspases. In this study we assayed for the activities of caspases 3, 8 (primary caspase of the extrinsic pathway), and 9 (primary caspase of the intrinsic pathway) in T27A cells incubated in the absence and presence of DHA. We found that caspase 3 activity was increased by 133%, caspase 8 by 128%, and caspase 9 by 196% compared to control cells, suggesting that DHA induces apoptosis via both the intrinsic and extrinsic pathways in these cells. We next addressed the question of whether fish cells, which have naturally high levels of DHA, are affected by exogenous DHA. We found that when fish cells (ZFL and CHSE lines) were incubated with DHA their growth rates were dramatically reduced, and that the concentration of DHA required to accomplish cell killing in fish cell lines was 20 times lower that that required to kill the tumor cells. These data suggest that fish cells are poised closer to the �DHA threshold� required to cause cell death. We are currently exploring the role of the caspases in the DHA-induced killing of fish cells.