Influence of acute hypoxia and radiation quality on cell survival

W Tinganelli,M Durante,W Kraft-Weyrather,C Schicker,N.-Y Ma,C Von Neubeck,A Maier

doi:10.1093/jrr/rrt065

Abstract

To measure the effect of acute oxygen depletion on cell survival for different types of radiation, experiments have been performed using Chinese hamster ovary (CHO) cells and RAT-1 rat prostate cancer cells. A special chamber has been developed to perform irradiations under different levels of oxygenation. The oxygen concentrations used were normoxia (air), hypoxia (94.5% N2, 5% CO2, 0.5% O2) and anoxia (95% N2, 5% CO2). Cells were exposed to X-rays and to C-, N- or O-ions with linear energy transfer (LET) values ranging from 100–160 keV/µm. The oxygen enhancement ratio (OER) and relative biological effectiveness (RBE) values have been calculated from the measured clonogenic survival curves. For both cell lines, the X-ray OER depended on the survival level. For particle irradiation, OER was not dependent on the survival level but decreased with increasing LET. The RBE of CHO cells under oxic conditions reached a plateau for LET values above 100 keV/µm, while it was still increasing under anoxia. In conclusion, the results demonstrated that our chamber could be used to measure radiosensitivity under intermediate hypoxia. Measurements suggest that ions heavier than carbon could be of additional advantage in the irradiation, especially of radioresistant hypoxic tumor regions.

Highlights

In clinical radiotherapy, hypoxia is a characteristic feature of locally advanced solid tumors [1, 2]
Cells were exposed to X-rays and to C, N- or O-ions with linear energy transfer (LET) values ranging from 100–160 keV/μm
The relative biological effectiveness (RBE) of Chinese hamster ovary (CHO) cells under oxic conditions reached a plateau for LET values above 100 keV/μm, while it was still increasing under anoxia

Summary

Introduction

Hypoxia is a characteristic feature of locally advanced solid tumors [1, 2]. Those hypoxic tumor cells are often responsible for local recurrences [3] and a source of metastases [4, 5], resulting in a poor prognosis [6]. At oxygen concentrations > 3% the full sensitizing effect is observed, while at lower concentrations, especially from 1% to 0.1%, a steep decrease in radiosensitivity is measured. For a long time OER was used as a dose-modifying factor, i.e. independent from the survival level, but recent measurements indicate a reduced i24

Methods

Results

Conclusion