Effect of oncogene transformation of rat embryo cells on cellular oxygen consumption and glycolysis.
We found an unique effect of oncogene transfections on rat embryo cell (REF) respiration, glycolysis and radiation response. Radioresistance, defined as an increase in Do, increases for REF cells transfected with v-myc or H-ras oncogenes. The combination of both oncogenes confers the maximal radioresistance. Our work shows inhibition of oxygen uptake when cells are transfected with v-myc or H-ras alone. However, oxygen uptake increases when cells are transfected simultaneously with v-myc + H-ras (3.7,2.1,2.8). A higher oxygen consumption results from increased utilization of pyruvate via the Kreb's cycle. Succinate stimulates cellular oxygen consumption. The maximum stimulation of oxygen consumption by succinate occurred with v-myc + H-ras transfected cells. The glycolysis of the transfected cells is also altered by the oncogenes. Our glycolytic measurements indicate the H-ras oncogene causes the largest stimulation of glycolysis. Our data shows that transfection with oncogenes has a major effect on cellular glycolysis, oxidative metabolism as well as the subsequent radiation response.
Biaglow
J E
JE
Department of Radiation Oncology, and Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104, USA.
Cerniglia
G
G
Tuttle
S
S
Bakanauskas
V
V
Stevens
C
C
McKenna
G
G
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002952:Citric Acid Cycle; D004622:Embryo, Mammalian; D016259:Genes, myc; D011905:Genes, ras; D006019:Glycolysis; D007700:Kinetics; D010101:Oxygen Consumption; D051381:Rats; D013386:Succinates / Q000378:metabolism; D014162:Transfection
D013386:Succinates