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

Purpose: To investigate the radiation sensitivity of asynchronous and synch ronized cancer cervix cells irradiated with low dose rates. Materials and methods: Cells were exposed to Co-60 gamma-rays at dose rates ranging from 0.33 to 0.94 Gy/h. Synchronized cells were obtained by collec ting detached mitotic cells after a shaking procedure. Cell survival was me asured as the ability of cells to form colonies. Cell-cycle distributions w ere calculated by computer analysis of a DNA histogram recorded by flow cyt ometry. Results: Irradiation of asynchronous cells at either 0.33 or 0.86 Gy/h resu lted in exponential dose-survival curves with equal alpha-values, i.e. same radiation sensitivity, when dose-survival data for irradiation periods les s than 20 h were considered, However, the radiation sensitivity was higher by a factor of two when analysing dose-survival data for irradiation period s exceeding 20 h. This increase in radiation sensitivity occurred when 80% of the cells accumulated in a pre-mitotic stage of the cell cycle. Irradiat ion of synchronized cell populations confirmed that these cells were a fact or 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 radiat ion doses exceeding 7 Gy due to pre-mitotic accumulation of cells during lo w dose-rate irradiation.