Abstract
Systems biology predicts that some properties result from altered relationships between components. Systems radiation biology asks not only how radiation affects specific components (i.e. cells) but also how these alterations affect interactions that maintain tissue integrity. While radiation can alter genomic sequence as a result of DNA damage, it can also induce signals that alter multicellular interactions and phenotypes that underpin carcinogenesis. Our previous studies characterized the composition of irradiated mouse tissues, identified transforming growth factor β1 (TGFβ) as a key cytokine activated by radiation, and developed novel models of radiation effects in both mice and cultured human epithelial cells. This presentation will focus on how TGFβ regulates the intrinsic DNA damage response, tissue composition and the carcinogenic effects of low dose radiation. Rather than being accessory or secondary to genetic damage, we propose that radiation induced signaling via TGFβ creates the critical context for cancer development.
Research funded by US DOE Low Dose Radiation Program
and NASA Specialized Center of Research
