Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Benzene is a common environmental pollutant found in cigarette smoke and fuel combustion. Research has indicated that increased exposure of pregnant mothers to benzene is associated with an increased occurrence of childhood leukemia in their offspring. Unfortunately, the reason for this increased occurrence of blood cancer is not completely understood. One way by which benzene is thought to be harmful is via its metabolism in the liver leading to the increased production of reactive compounds, termed reactive oxygen species (ROS). These ROS can react with different molecules within cells, including critical proteins as well as DNA. Pregnant mice exposed to benzene have been shown to lead to an increased occurrence of tumour formation in the offspring one year post-exposure, providing a valuable animal model to study this process. To determine whether ROS are involved, I will expose pregnant mice to benzene, or benzene plus an antioxidative enzyme, catalase, which is known to quench certain ROS. If treatment with catalase decreases the occurrence of tumour formation in offspring, this will suggest that increased ROS plays an important role in benzene carcinogenesis. To further examine the role of ROS in carcinogenicity of benzene, I will examine the role of benzene in altering cell-signalling pathways. Some of the proteins that ROS can interact with are proteins involved in explicit cellular signals, important for normal cellular functioning. Myeloid blood cells will be exposed to either benzene or benzene plus catalase, to determine whether benzene leads to changes in these signalling pathways, and whether this change is attenuated by treatment with catalase. If the results of both of these studies show that catalase reduces the benzene-induced damage, this would suggest that antioxidants could be an important component of a treatment to prevent the development of childhood leukemia in mothers with increased exposure to benzene.