Grant: Operating Grant - PA: Alberta Cancer Foundation - Research (bridge funding)

Project summary: Arsenic is now recognized as one of the most important environmental agents causing cancers of the skin, bladder, and lungs. However, it is uncertain what level of arsenic is acceptable because scientists don't know how arsenic causes these cancers. The primary objective of this study is to improve our understanding of how arsenic causes cancer. Specifically, we will investigate how arsenic interacts with other cancer-causing agents and contributes to cancers. Previous Research: Many carcinogens act by causing damage to our genetic material (DNA), but this does not appear to be the case for arsenic. This research team and others have shown that arsenic interferes with the repair of DNA damage caused by other agents, such as chemicals present in cigarette smoke. These findings are consistent with population surveys showing the synergistic interactions between arsenic exposure and cigarette smoking in lung cancer risk. Project description: The research team, using their complementary expertise, will study how arsenic affects the cellular machinery to repair DNA damage. The team will examine the effect of arsenic on the repair of DNA damage produced by a chemical found in cigarette smoke and by ultraviolet radiation because of the important role of arsenic exposure in causing lung and skin cancer. They will focus on how arsenic influences an antitumor molecule, called p53, and other associated proteins, which help to regulate the cellular DNA repair machinery. Impact & relevance: The study will provide mechanistic insight necessary for an improved understanding of the carcinogenic effects of arsenic. By understanding the causal effect of arsenic, regulatory agencies would be able to develop scientifically sound guidelines to prevent or reduce cancers induced by arsenic. The fundamental understanding of DNA repair, an essential process that protects against cancer, will also contribute to cancer research in general.