Inverse dose-rate effect due to pre-mitotic accumulation during continuous low dose-rate irradiation of cervix carcinoma cells.
OBJECTIVE
To investigate the radiation sensitivity of asynchronous and synchronized cancer cervix cells irradiated with low dose rates.


METHODS
Cells were exposed to 60Co gamma-rays at dose rates ranging from 0.33 to 0.94 Gy/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 0.86 Gy/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 7 Gy due to pre-mitotic accumulation of cells during low dose-rate irradiation.
Department of Cell Biology, The Norwegian Radium Hospital, Oslo. tfurre@ulrik.uio.no
T
T
Furre
M
M
Koritzinsky
D R
DR
Olsen
E O
EO
Pettersen
D001918:Brachytherapy; D002453:Cell Cycle / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*