Effect of dose-rate and irradiation geometry on the biological response of normal cells and cancer cells under radiotherapeutic conditions.

Biological efficacy of radiation depends on its energy, dose, dose rate, and on the type of cell irradiated. Changes in the radiation-energy spectrum due to passage through absorbing and scattering media affect the variability of biological responses of the cells. We investigated the impact of photon-radiation dose rate on the biological response of both normal and cancer cells in culture exposed to radiation in various positions (relative to the axis of the radiation beam) and depth of the absorbing medium (water). Human cancer cells (A549 and HCT116) as well as normal human cells (BEAS-2B) were placed in a water phantom at different medium depths (3 cm, 15 cm) and exposed to 6-MV photon radiation delivered at a beam rate of either 100 or 600 MU/min (Monitor Units per minute). The applied dose was 5 Gy. Cells were exposed in the axis and four cm outside the radiation field. Radiation-induced genetic changes were estimated as frequency of micro-nucleated and apopototic-like cells, by use of a cytokinesis-block micronucleus test. A smaller dose rate induced more severe cytogenetic damage (formation of micro-nucleated and apoptotic cells) than a higher dose rate, both in normal and in cancer cells. More micro-nucleated and apoptotic cells were formed at larger depth than at smaller depth. This holds true for both the normal and the two types of cancer cell investigated. The extent of cytogenetic damage arising in cells placed outside the irradiation field is independent of positioning depth and dose rate. Exposure of cells to smaller dose rates and larger depths in water medium resulted in a better ratio of cytogenetic damage to cancer cells irradiated in the beam axis vs damage to normal cells exposed outside the radiation field.