Studies of iron uptake and regulation in animal cells and affects of novel iron chelators

Iron is needed for the growth of all animal cells, being necessary for the proper function of many differentenzyme systems and the expression of certain important genes, as well as for the production of oxygen radicalsthat help defend against microorganisms. Given the key roles for iron in cell growth, metabolism, and hostdefence, a better understanding of iron uptake and its regulation by different animal cell types could provideimportant new information as to the functioning of animal cells under normal and disease conditions. However,studies of iron requirements and the effects of iron withdrawal on animal cells have been limited by the lack ofsuitable model cell systems in which iron supply can be fully controlled and the lack of iron-withdrawingagents that are more selective in their action. Chelation Partners Incorporated (CPI) has developed a newfamily of highly selective iron-withdrawing agents (iron chelators), and is interested to determine whether theseagents are active with animal cells. In this collaborative research project the Hoskin laboratory will use noveliron-withdrawing agents from CPI to compare specific iron requirements and iron uptake in mouse versushuman cells of differing types. Counterpart malignant cell lines will be used to test the hypothesis that cells thatgrow continuously may have higher and/or more continuous iron requirements. The effect of iron withdrawalon the activity of other cell growth inhibitors will also be determined. The proposed research will yield newinsights into iron regulation and dysregulation in animal cells, leading to the identification of potential newpathways for controlling cell growth at the level of iron requirements. This new information will haveimportant biotechnology and biomedical applications for Canada.