Involvement of energy metabolism in the production of 'bystander effects' by radiation

These experiments were done to determine if interference with energy metabo lism and REDOX biochemistry during low LET radiation exposure would alter t he ability of medium harvested from the irradiated cells to induce a bystan der effect in unirradiated cells. Human keratinocyte cells and CHO-K1 mutan t cell lines were irradiated using cobalt 60. Clonogenic assays were used t o determine the reproductive death of the cells exposed to direct irradiati on or medium from irradiated cells. The persistence in progeny was also exa mined. Use of apoptosis inhibitors or medium from the LDH or G6PD null cell lines, reduced or prevented the bystander effect. Transfection with G6PD r ecovered the effect. Treatment with anti-oxidant substances, L-lactate and L-deprenyl prevented bystander factor associated cell kill. The lactate ana logue, oxamate, was less effective. Data from experiments where media harve sted from the different cell lines was exchanged suggest that signal produc tion and cellular response may involve different mechanisms. The effects on exposed cells were transmitted to progeny which also showed excessive leve ls of cell death for several generations. The results suggest that energy/R EDOX metabolism may be involved in the expression of a radiation induced by stander response. Given the aberrant energy metabolism in tumour cells, thi s may have implications for dose escalation in radiotherapy. (C) 2000 Cance r Research Campaign.