Inverse dose-rate effect due to pre-mitotic accumulation during continuous low dose-rate irradiation of cervix carcinoma cells

Abstract

Purpose: To investigate the radiation sensitivity of asynchronous and synchronized cancer cervix cells irradiated with low dose rates. Materials and methods: Cells were exposed to 60Co gamma-rays at dose rates ranging from 0.33 to 0.94Gy/h. Synchronized cells were obtained by collecting detached mitotic cells after a shaking procedure. Cell survival was measured as the ability of cells to form colonies. Cell-cycle distributions were calculated by computer analysis of a DNA histogram recorded by flow cytometry. Results: Irradiation of asynchronous cells at either 0.33 or 0.86Gy/h resulted in exponential dose-survival curves with equal alpha-values, i.e. same radiation sensitivity, when dose-survival data for irradiation periods less than 20h were considered. However, the radiation sensitivity was higher by a factor of two when analysing dose-survival data for irradiation periods exceeding 20h. This increase in radiation sensitivity occurred when 80% of the cells accumulated in a pre-mitotic stage of the cell cycle. Irradiation of synchronized cell populations confirmed that these cells were a factor of two more sensitive to radiation in G2 than in G1. Conclusions: An inverse dose-rate effect, i.e. more efficient inactivation of cells at lower rather than at higher dose rates, was observed for radiation doses exceeding 7Gy due to pre-mitotic accumulation of cells during low dose-rate irradiation.