Grant: Operating Grant

To protect our bodies from daily exposure to cancer causing chemicals, cells have protective pathways in place. These include surface (or membrane) protein pumps that can prevent harmful chemicals getting into cells. If chemicals by-pass the pumps and enter the cell, metabolic enzymes (or proteins that speed up change within the cell) can modify them to a less harmful more water soluble form, that must be pumped out across the cell membrane. We are investigating how protein pumps and metabolic enzymes protect cells from the cancer causing environmental poison arsenic. We will investigate how these proteins function and how slight variations in their genetic code can influence their ability to protect cells from arsenic. Characterization of metabolic pathways and protein pumps involved in preventing the accumulation of cancer causing chemicals, such as arsenic, lays the foundation for identifying interindividual gene differences that could predispose people to chemically-induced cancers. This is critical for the development of strategies to prevent arsenic-induced cancers and toxicities. Furthermore, although these protein pumps and metabolic pathways are protective in healthy tissue they can also protect cancer cells and make tumours unresponsive to cancer drug treatment. Thus, understanding how these proteins function is important not only for effective cancer prevention, but also cancer treatment strategies.