Modelling of cell killing due to sparsely ionizing radiation in normoxic and hypoxic conditions and an extension to high LET radiation

Abstract

Purpose: An approach for describing cell killing with sparsely ionizing radiation in normoxic and hypoxic conditions based on the initial number of randomly distributed DNA double-strand breaks (DSB) is proposed. An extension of the model to high linear energy transfer (LET) radiation is also presented.

Materials and methods: The model is based on the probabilities that a given DNA giant loop has one DSB or at least two DSB. A linear combination of these two classes of damage gives the mean number of lethal lesions. When coupled with a proper modelling of the spatial distribution of DSB from ion tracks, the formalism can be used to predict cell response to high LET radiation in aerobic conditions.

Results: Survival data for sparsely ionizing radiation of cell lines in normoxic/hypoxic conditions were satisfactorily fitted with the proposed parametrization. It is shown that for dose ranges up to about 10 Gy, the model describes tested experimental survival data as good as the linear-quadratic model does. The high LET extension yields a reasonable agreement with data in aerobic conditions.

Conclusions: A new survival model has been introduced that is able to describe the most relevant features of cellular dose-response postulating two damage classes.

Keywords::

• Radiation
• hypoxia
• clonogenic cell survival

Note

Acknowledgements

The authors would like to thank M. Suzuki, T. Kanai and K. Ando for making the cell survival experimental data kindly available in electronic format.

Declaration of interest

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

Notes

1. As suggested by Carlson et al. (2011), we have used the term hypoxia reduction factor rather than oxygen enhancement ratio (OER) to quantify the effects of oxygen concentration on DNA damage and cell death. The factor was first introduced in Carlson et al. (2011) to scale the LQ parameters in a similar method as done by Carlson et al. (2006). Stewart et al. (2011) extended the use of this terminology to quantify the effects of oxygen concentration on DNA damage and cell death.