Interaction of low and high LET radiation in TK6 cells-mechanistic aspects and significance for radiation protection

Most environmental, occupational and medical exposures to ionising radiation are associated with a simultaneous action of different radiation types. An open question remains whether radiations of different qualities interact with each other to yield effects stronger than expected based on the assumption of additivity. It is possible that DNA damage induced by high linear energy transfer (LET) radiation will lead to an opening of the chromatin structure making the DNA more susceptible to attack by reactive oxygen species (ROS) generated by the low LET radiation. In such case, the effect of mixed beams should be strongly expressed in cells that are sensitive to ROS. The present investigation was carried out to test if cells with an impaired capacity to handle oxidative stress are particularly sensitive to the effect of mixed beams of alpha particles and x-rays. Clonogenic cell survival curves and mutant frequencies were analysed in TK6 wild type (wt) cells and in TK6 cells with a knocked down hMYH glycosylase. The results showed a synergistic effect of mixed beams on clonogenic cell survival of TK6(wt) but not TK6(MYH)-cells. The frequencies of mutants showed a high degree of interexperimental variability without any indications for synergistic effects of mixed beams. TK6(MYH)-cells were generally more tolerant to radiation exposure with respect to clonogenic cell survival but showed a strong increase in mutant frequency. The results demonstrate that exposure of wt cells to a mixed beam of alpha particles and x-rays leads to a detrimental effect which is stronger than expected based on the assumption of additivity. The role of oxidative stress in the reaction of cells to mixed beams remains unclear.