PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 24, 2002
Poster Session 31 Cytoskeleton/Nuclear Matrix/Extracellular Matrix
Room: Nevada Exhibition Center

(P36-359) The role of cell environment, reactive oxygen species and transforming growth factor beta in response to ionizing radiation.

Tatum, Owatha^*,1, Gadbois, Donna¹, ¹ Los Alamos National Laboratory, Los Alamos, NM

ABSTRACT-
Much of radiation cell cycle research is based on the idea that the purpose of radiation-induced cell cycle delays or checkpoints is to allow time for DNA damage repair before cell division. This would reduce the amount of inherited chromosomal damage and, perhaps, eliminate neoplasia in daughter cells. A limitation of this model is that it does not consider that the radiation stress response will reflect the physiological function of different cell types and the cell environment. Our research develops a paradigm for the radiation stress response of human fibroblasts that includes both the function and the cellular environment of the fibroblast. It has been demonstrated that human fibroblasts do not pause in the G₁ phase and then re-enter the cell cycle after repairing DNA damage. Rather, the irradiated fibroblasts undergo a permanent G₁ arrest that results in the expression of smooth muscle -actin, a characteristic of the differentiated myofibroblasts. These observations relate to the fact that fibroblasts play a central role in wound healing, scar formation and radiation fibrosis. During these processes, fibroblasts accumulate at the site of inflammation, differentiate to myofibroblasts and produce copious amounts of extracellular matrix (ECM) and extracellular factors. These extracellular factors and ECM molecules function as signals for neighboring cell types, such as epithelial cells. However, we propose that these signals also act on the fibroblasts themselves to sustain cell cycle arrest and induce myofibroblast differentiation. Here, we report the influence of ECM, oxidative factors, and the TGF-1 pathway on the radiation cell cycle arrest and differentiation of human fibroblasts.

KEYWORDS: extracellular matrix, alpha-actin, myofibroblast, radiation fibrosis