Cell inactivation by combined low dose-rate irradiation and intermittent hypoxia

Abstract

Purpose: To investigate in detail the earlier observed combined effect of low dose-rate β-irradiation delivered at a dose-rate of 15 mGy/h and continued intermittent hypoxia that leads to extensive cell death after approximately 3–6 weeks.

Material and methods: Continuous low dose-rate β-irradiation at a dose rate of 15, 1.5 or 0.6 mGy/h was given by incorporation of [³H]-labelled valine into cellular protein. The cells were cultivated in an atmosphere with 4% O₂ using an INVIVO₂ hypoxia glove box. Clonogenic capacity, cell-cycle distribution and cellular respiration were monitored throughout the experiments.

Results: After 3–6 weeks most cells died in response to the combined treatment, giving a surviving fraction of only 1–2%. However, on continued cultivation a few cells survived and restarted proliferation as the cellular oxygen supply increased with the reduced cell number. Irradiating the T-47D cells grown in an atmosphere with 4% O₂ at dose-rates 10 and 25 times lower than 15 mGy/h did not have a pronounced effect on the clonogenic capacity with surviving fractions of 60–80%.

Conclusions: Treatment of T-47D cells with low dose-rate β-irradiation leads to a specific effect on intermittent hypoxic cells, inactivating more than 98% of the cells in the population. Given improved oxygen conditions, the few surviving cells can restart their proliferation.

Keywords::

• T-47D cells
• low dose-rate irradiation
• β-irradiation
• hypoxia

Declaration of interest

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

This work was supported by EU grant No. 222741 (METOXIA); the Research Council of Norway and the Norwegian Cancer Society.