Involvement of energy metabolism in the production of 'bystander effects' by radiation.
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.
Mothersill
C
C
Radiation Science Centre, Dublin Institute of Technology, Ireland.
Stamato
T D
TD
Perez
M L
ML
Cummins
R
R
Mooney
R
R
Seymour
C B
CB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells / Q000187:drug effects / Q000528:radiation effects; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line / Q000528:radiation effects; D006224:Cricetinae; D017077:Culture Media, Conditioned; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007302:Insect Repellents / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D009930:Organic Chemicals; D010084:Oxidation-Reduction; D011836:Radiation Tolerance
D017077:Culture Media, Conditioned; D007302:Insect Repellents; D009930:Organic Chemicals; D019344:Lactic Acid; C048603:oxamate (repellent); D007770:L-Lactate Dehydrogenase