Mechanisms of the elimination of low dose hyper-radiosensitivity in T-47D cells by low dose-rate priming

Abstract

Purpose: To investigate the mechanisms of elimination of low-dose hyper-radiosensitivity (HRS) in T-47D cells induced by 0.3 Gy low dose-rate (LDR) priming.

Materials and methods: The mitotic ratio was measured using mitotic marker histone H3 phosphorylation in LDR primed as well as untreated T-47D cells. The HRS response in unprimed cells receiving medium which was irradiated after being harvested from unprimed cells was measured with or without serum present during cell conditioning. 4,6-benzylidene-D-glucose (BG) was used to inhibit protein synthesis during LDR priming.

Results: LDR primed T-47D cells were HRS-deficient and showed a decrease in mitotic ratio with increasing dose while unprimed, i.e., HRS-competent T-47D cells, showed no decrease in mitotic ratio for doses in the HRS-range. HRS was eliminated in LDR primed cells, in cells receiving medium transfer from LDR primed cells, and in cells receiving LDR irradiated medium harvested from unprimed cells. The efficacy of the transferred medium depended on the presence of serum during cell conditioning. LDR priming eliminated HRS even in the presence of protein synthesis inhibitor BG.

Conclusions: LDR priming of T-47D cells as well as LDR priming of medium conditioned on T-47D cells induce a factor in the medium which cause the early G₂-checkpoint to be activated in recipient cells by doses normally in the HRS dose-range.

Keywords:

• T-47D cells
• low dose hyper-radiosensitivity
• low dose-rate irradiation
• medium transfer

Acknowledgments

This work was supported by EU grant No. 502932 (EUROXY); the Research Council of Norway and the Norwegian Cancer Society. The skillful technical assistance of Kirsti Solberg Landsverk, The Norwegian Radium Hospital is highly appreciated.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.