Biaglow J E, Cerniglia G, Tuttle S, Bakanauskas V, Stevens C, McKenna G
Department of Radiation Oncology, and Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104, USA.
Biochem Biophys Res Commun. 1997 Jun 27;235(3):739-42. doi: 10.1006/bbrc.1997.6835.
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.
我们发现癌基因转染对大鼠胚胎细胞(REF)的呼吸、糖酵解和辐射反应具有独特影响。辐射抗性定义为Do值增加,对于用v-myc或H-ras癌基因转染的REF细胞,辐射抗性增加。两种癌基因的组合赋予最大的辐射抗性。我们的研究表明,单独用v-myc或H-ras转染细胞时,摄氧量会受到抑制。然而,当细胞同时用v-myc + H-ras转染时,摄氧量增加(分别为3.7、2.1、2.8)。通过三羧酸循环增加丙酮酸的利用导致更高的耗氧量。琥珀酸刺激细胞耗氧量。琥珀酸对耗氧量的最大刺激作用出现在用v-myc + H-ras转染的细胞中。转染细胞的糖酵解也因癌基因而改变。我们的糖酵解测量表明,H-ras癌基因对糖酵解的刺激作用最大。我们的数据表明,癌基因转染对细胞糖酵解、氧化代谢以及随后的辐射反应有重大影响。