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Abstract

These experiments were done to determine if interference with energy metabolism and REDOX biochemistry during low LET radiation exposure would alter the ability of medium harvested from the irradiated cells to induce a bystander effect in unirradiated cells. Human keratinocyte cells and CHO-K1 mutant cell lines were irradiated using cobalt 60. Clonogenic assays were used to determine the reproductive death of the cells exposed to direct irradiation or medium from irradiated cells. The persistence in progeny was also examined. Use of apoptosis inhibitors or medium from the LDH or G6PD null cell lines, reduced or prevented the bystander effect. Transfection with G6PD recovered the effect. Treatment with anti-oxidant substances, L -lactate and L -deprenyl prevented bystander factor associated cell kill. The lactate analogue, oxamate, was less effective. Data from experiments where media harvested from the different cell lines was exchanged suggest that signal production and cellular response may involve different mechanisms. The effects on exposed cells were transmitted to progeny which also showed excessive levels of cell death for several generations. The results suggest that energy/REDOX metabolism may be involved in the expression of a radiation induced bystander response. Given the aberrant energy metabolism in tumour cells, this may have implications for dose escalation in radiotherapy. © 2000 Cancer Research Campaign

Gap Junction Communication and the Propagation of Bystander Effects Induced by Microbeam Irradiation in Human Fibroblast Cultures: The Impact of Radiation Quality

“…These results indicated that the cross section for inducing chromosomal damage by α particles was much larger than the nucleus or the cell itself. These findings were subsequently confirmed with a variety of biological endpoints such as cell killing, micronucleus (MN) formation, mutation, cell cycle arrest, oncogenic transformation, and changes in the levels of mRNA and proteins (2–17). The bystander effect has been observed in different types of cells exposed to various radiations.…”

“…Notably, the progeny of bystander cells that were co-cultured with cells irradiated with high-LET iron, but not low-LET protons, and allowed to grow for 20 generations showed a decrease in cloning efficiency, an increase in MN formation and higher levels of oxidative stress (44), and were more prone to neoplastic transformation than respective controls (45). Therefore, strong evidence indicates short- and long-term effects in bystander cells depend on radiation quality (1–17, 19–25, 42–47). …”

“…In contrast, under low-LET irradiation conditions (Figs. 2 and 3), secretion of a cytotoxic factor (e.g., long-lived oxidizing molecules, cytokines) may be involved (4, 17, 20, 44–47). In particular, pathways that perturb oxidative metabolism are likely to be important in both mechanisms (4, 20, 39, 49, 50).…”

“…The bystander effect has been observed in different types of cells exposed to various radiations. Both high- and low-LET radiation have been shown to induce a bystander response (1–17). However, the observations were not universal.…”

Energy Metabolism in a Matched Model of Radiation Resistance for Head and Neck Squamous Cell Cancer

“…However, an additive or synergistic effect, when used in combination with inhibitors of cellular energy metabolism, was not evident from the studies reported here suggesting either: 1. masking of the radiation-induced cell death due to the much stronger effects of energy deprivation; or 2. dependence of radiation effects on energy metabolism. We favor the second scenario based on the known mechanisms of radiation-induced ROS and ROS amplification in time (41) and data showing an inhibition of the radiation-induced bystander effects and cell death in G6PD null cells (42). …”