title: Mitigation of radiation-induced lung injury by genistein and EUK-207.
abstract: OBJECTIVE
  We examined the effects of genistein and/or Eukarion (EUK)-207 on radiation-induced lung damage and investigated whether treatment for 0-14 weeks (wks) post-irradiation (PI) would mitigate late lung injury.
  
  
  METHODS
  The lungs of female Sprague-Dawley (SD) rats were irradiated with 10 Gy. EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (post irradiation [PI]) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1β, IL-6, Tumor necrosis factor (TNF)-α and Transforming growth factor (TGF)-β1, and macrophage activation were analyzed by immunohistochemistry.
  
  
  RESULTS
  Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4-14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines.
  
  
  CONCLUSIONS
  Genistein and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI.
authors.affiliation: Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Javed
authors.initials: J
authors.lastname: Mahmood
authors.forename: Salomeh
authors.initials: S
authors.lastname: Jelveh
authors.forename: Victoria
authors.initials: V
authors.lastname: Calveley
authors.forename: Asif
authors.initials: A
authors.lastname: Zaidi
authors.forename: Susan R
authors.initials: SR
authors.lastname: Doctrow
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
mesh_terms: D000818:Animals; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000503:physiopathology*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000528:radiation effects*; D016896:Treatment Outcome
chemical_list: C476761:EUK 207; D009942:Organometallic Compounds; D011837:Radiation-Protective Agents; D019833:Genistein