OHSU-MIT-FHCRC DNA Alkylation in Neurodegenerative Disease and Cancer

This 3-CRM Star Project employs wild-type and DNA-repair knock-out mice to define differential genome responses of adult liver and brain tissues to a range of alkylating agents linked to cancer and neurodegeneration, respectively. We hypothesize that the genome of adult mice will show differential responses by tissue type and method of alkylation. Since hepatic cells repair alkylation DNA adducts more rapidly than non-dividing neurons, we anticipate a differential gene response in liver versus brain tissue independent of the fact that these tissues are certain to have different basal transcriptional profiles. This project will allow us simultaneously to examine a scientific question relevant to exposures to environmental agents as we address critical technical issues pertinent to the TRC mission .