Grant: Operating Grant

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 gain a mechanistic understanding of how arsenic causes cancer. Specifically, this study 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 ultraviolet light and 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, is now studying how arsenic affects the cellular machinery to repair the genetic damage. In particular, they will study how arsenic influences an antitumor molecule, called p53, and other proteins associated with it. They will further confirm their findings by extending the study to examine the effect of arsenic on the repair of DNA damage using experimental animals. Impact & relevance: The study will provide the mechanistic insight necessary to 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 and measures to prevent and reduce cancers, particularly those induced by arsenic. The fundamental understanding of DNA repair, an essential process that protects against cancer, will also contribute to cancer research in general.