Presentation: Overview of Project 2
One reason that individuals vary in how susceptible they are to toxic effects of chemicals is because they differ in genes that are affected by the chemicals. Cancers and other disease can arise from such interactions between environmental agents and genes. How agents affect the cell is likely to influence which genes that are affected. At present, understanding of how many chemicals affect cells is limited. This project will use yeast to investigate the targets for toxic chemicals in cells. The project takes advantage of the fact that many aspects of human metabolism are also present in yeast. The project will use methods called parallel deletion analysis (PDA) and RNA interference (RNAi) to look at the relative importance of individual genes to contributing to susceptibility. The project includes some chemicals that are converted to a more toxic form in the human body (through "metabolic activation"), such as benzene and polycyclic aromatic hydrocarbons (PAHs), and some metals that are already in a toxic form when they enter the human body, such as arsenic and cadmium. The method will identify candidates for genes that contribute to susceptibility to environmental agents. These will then be tested in human cells lines to determine their sensitivity to cytotoxicity, genotoxicity and epigenetic effects. Investigators hope that this will identify genes that contribute to human susceptibility to chemicals and their metabolites.