title: Glucocorticoids modulate tumor radiation response through a decrease in tumor oxygen consumption.
abstract: OBJECTIVE
  We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO(2)) through inhibition of mitochondrial respiration.
  
  
  METHODS
  The effect of three glucocorticoids (hydrocortisone, dexamethasone, and prednisolone) on pO(2) was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO(2) (t(max), 30 min after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO(2) measurements were done using electron paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo glucocorticoid administration was measured using high-frequency electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging.
  
  
  RESULTS
  All glucocorticoids tested caused a rapid increase in pO(2). At t(max), tumor perfusion decreased, indicating that the increase in pO(2) was not caused by an increase in oxygen supply. Also at t(max), global oxygen consumption decreased. When irradiation (25 Gy) was applied at t(max), the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7).
  
  
  CONCLUSIONS
  These results show the potential usefulness of the administration of glucocorticoids before irradiation.
authors.affiliation: Laboratories of Medicinal Chemistry and Radiopharmacy, Université Catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Crokart
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
authors.forename: Christine
authors.initials: C
authors.lastname: Baudelet
authors.forename: Gregory O
authors.initials: GO
authors.lastname: Cron
authors.forename: Julie
authors.initials: J
authors.lastname: Hotton
authors.forename: Kim
authors.initials: K
authors.lastname: Radermacher
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Nelson
authors.initials: N
authors.lastname: Beghein
authors.forename: Philippe
authors.initials: P
authors.lastname: Martinive
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D002470:Cell Survival; D003131:Combined Modality Therapy; D004578:Electron Spin Resonance Spectroscopy; D005938:Glucocorticoids / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology; D008113:Liver Neoplasms / Q000628:therapy; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D009374:Neoplasms, Experimental / Q000628:therapy; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010477:Perfusion; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D010100:Oxygen; D006854:Hydrocortisone