The effects of 2-deoxyglucose and amino-oxyacetic acid on the radiation response of mammalian cells in vitro.
Cells use substrates such as glucose and glutamine to provide energy for repair of radiation damage. Glutaminolysis and glycolysis were inhibited by aminooxyacetic acid (AOAA) and 2-deoxyglucose (2DG), respectively, to inhibit metabolism of these substrates in order to determine the effect on radiation response of CHO-K1 cells in vitro. Exposure to treatments which inhibit energy metabolism resulted in alterations in radiosensitivity and, in general, a reduction in cellular recovery rate after y-irradiation but varied with regard to the extent of recovery. The greatest inhibition of recovery relative to that in normal culture medium was found with medium which lacked glucose and glutamine and contained 2DG and AOAA. In contrast, medium lacking glucose and glutamine without the addition of inhibitors resulted in an increase in recovery. It is proposed that the efficiency of energy pathways such as glycolysis and glutaminolysis and their interaction are determinants of both radiosensitivity and recovery.
Hunter
A J
AJ
Department of Radiation Oncology, University of Cape Town/Groote Schuur Hospital, South Africa.
Blekkenhorst
G H
GH
D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D016466:CHO Cells; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D003470:Culture Media; D004260:DNA Repair; D003847:Deoxyglucose / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D007773:Lactates / Q000378:metabolism; D013997:Time Factors
D000963:Antimetabolites; D003470:Culture Media; D004791:Enzyme Inhibitors; D007773:Lactates; D005973:Glutamine; D000625:Aminooxyacetic Acid; D003847:Deoxyglucose; D005947:Glucose