Development of an in vivo assay for detection of non-targeted radiation effects

An adaptive response may be defined as the effect of a small priming dose of radiation modifying the anticipated cellular response of the same tissues so as to alter the predicted response to a larger dose of radiation. We and others have demonstrated that at low radiation doses (less than 0.5 Gy) the lethal and mutational effect of the radiation is mainly, possibly entirely, due to the non-targeted effects. This is the dose range for priming doses in adaptive response protocols. In an associated presentation from our group, we demonstrate that the adaptive response may be explicable as a non targeted (bystander) response. In this paper we present data from exposed human patients, showing that a simple assay using blood can demonstrate variation in the extent and type of non-targeted effects and that exposure to radiation can modulate the subsequent non-targeted response to a later dose. Patients undergoing radiotherapy treatment for cancer gave blood samples immediately after the first dose, midway during and six weeks after therapy. The serum from these samples was harvested, diluted in tissue culture medium and added to reporter cells. The toxicity or growth promoting activity of the serum was measured using a clonogenic assay coupled with immunocytochemical measurement of various proteins involved in apoptosis or growth. There is already evidence that bystander effects are controlled by both genetic and epigenetic (lifestyle) factors. These data could support the development of a simple blood based assay to predict overall response of human subjects to low doses of radiation taking all the low dose factors into account.