title: Glycolysis-related gene induction and ATP reduction during fractionated irradiation. Markers for radiation responsiveness of human tumor xenografts.
abstract: OBJECTIVE
  Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity.
  
  
  METHODS
  Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR.
  
  
  RESULTS
  Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors.
  
  
  CONCLUSIONS
  Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment.
authors.affiliation: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128, Mainz, Germany. goetze@uni-mainz.de
authors.forename: K
authors.initials: K
authors.lastname: Goetze
authors.forename: S S
authors.initials: SS
authors.lastname: Meyer
authors.forename: A
authors.initials: A
authors.lastname: Yaromina
authors.forename: D
authors.initials: D
authors.lastname: Zips
authors.forename: M
authors.initials: M
authors.lastname: Baumann
authors.forename: W
authors.initials: W
authors.lastname: Mueller-Klieser
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006019:Glycolysis / Q000235:genetics / Q000528:radiation effects*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010084:Oxidation-Reduction / Q000187:drug effects; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019344:Lactic Acid; D000255:Adenosine Triphosphate