DOE Low Dose Radiation Research Program Workshop I Abstracts November 10-12, 1999, Washington, D.C.

29. The Role of the Number and Spacing of Electron Tracks on the Consequences of Low Dose Irradiation

Leslie A. Braby and J. R. Ford
Nuclear Engineering, Texas A&M University, 129 Zachry, College Station, TX 77843-3133
labraby@tamu.edu

Summary: Biological mechanisms which may influence the health risks resulting from very low dose radiation exposures will be investigated using a collimated beam of electrons to simulate the irradiation patterns occurring with low dose exposures.

Abstract: Ionizing radiation produces a variety of free radicals and chemical products which react to produce the same types of oxidative damage in a mammalian cell as produced by the normal metabolic activity of the cell. However, the damage produced by radiation is distributed differently in time and space and may trigger different repair mechanisms or different changes in the growth and differentiation of cells than those triggered by metabolic products. The health risk resulting from a low dose of radiation is currently estimated using the assumption that cells respond individually to radiation induced damage without influence of neighboring cells. Considering how efficiently cells deal with metabolic damage and that cell communication is involved in many growth regulation processes, it seems unlikely that cells would respond independently to irradiation. If they do not react independently, it is likely that the current use of a linear extrapolation to low doses significantly overestimates the risk.

The objective of this project is to evaluate the differences in the response to cells as a function of spatial and temporal distribution of radiation-induced damage. Specifically, we will: (1) Test the hypothesis that normal human epithelial cells transmit signals to neighboring cells in response to increased levels of oxidative damage produced by low-LET radiation. (2) Test the hypothesis that the probability of such a signal being received by an adjacent cell is a linear function of the energy deposited in the irradiated cell. (3) Test the hypothesis that the probability of each specific effect in an unirradiated cell is increased in proportion to the number of neighboring cells with elevated oxidative damage levels. And, (4) test the assumption that the signal is passed from cell to cell, but the intensity (probability of causing an effect) decreases in proportion to the distance transmitted. Increased repair related protein expression, apoptosis, and changes in cyclin proteins in neighboring unirradiated cells will be taken as evidence for receipt of a radiation induced signal from a neighboring cell.

Evaluation of the effects of temporal and spatial distribution of damage will be obtained by irradiating selected portions of monolayer cultures with an electron microbeam, delivering individual and counted numbers of electrons simulating beta particles and the secondaries of X- and gamma-ray irradiation to specified portions of the cell culture. The patterns of energy deposition produced by electron tracks in tissues will be simulated, to the extent possible, in the two dimensional tissue culture environment.

This controlled irradiation will make it possible to determine the magnitude of the effect of interaction between cells, and to evaluate the range of the signal which produces this interaction. The apoptotic response of irradiated and unirradiated cells, as well as changes in the expression and localization of repair and cell-cycle control related molecules, will be determined in order to evaluate the validity of linear extrapolations to low doses.