The Bystander Response in C3H 10T Cells: The Influence of Cell-to-Cell Contact

Although radiation-induced heritable damage in mamma-lian cells was thought to result from the direct interaction of radiation with DNA, it is now accepted that biological effects may occur in cells that were not themselves traversed by ion-izing radiation but are close to those that were. However, little is known about the mechanism underlying such a bystander effect, although cell-to-cell communication is thought to be of importance. Previous work using the Columbia microbeam demonstrated a significant bystander effect for clonogenic sur-vival and oncogenic transformation in C3H 10T cells. The present study was undertaken to assess the importance of the degree of cell-to-cell contact at the time of irradiation on the magnitude of this bystander effect by varying the cell density. When 10 % of cells were exposed to a range of 2–12 a parti-cles, a significantly greater number of cells (P, 0.0001) were inactivated when cells were irradiated at high density (.90% in contact with neighbors) than at low density (,10 % in con-tact). In addition, the oncogenic transformation frequency was significantly higher in high-density cultures (P, 0.0004). These results suggest that when a cell is hit by radiation, the transmission of the bystander signal through cell-to-cell con-tact is an important mediator of the effect, implicating the involvement of intracellular communication through ga