title: Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin.
abstract: OBJECTIVE
  Radioprotection and mitigation effects of the antioxidants, Eukarion (EUK)-207, curcumin, and the curcumin analogs D12 and D68, on radiation-induced DNA damage or lipid peroxidation in murine skin were investigated. These antioxidants were studied because they have been previously reported to protect or mitigate against radiation-induced skin reactions.
  
  
  METHODS
  DNA damage was assessed using two different assays. A cytokinesis-blocked micronucleus (MN) assay was performed on primary skin fibroblasts harvested from the skin of C3H/HeJ male mice 1 day, 1 week and 4 weeks after 5 Gy or 10 Gy irradiation. Local skin or whole body irradiation (100 kVp X-rays or caesium (Cs)-137 γ-rays respectively) was performed. DNA damage was further quantified in keratinocytes by immunofluorescence staining of γ-histone 2AX (γ-H2AX) foci in formalin-fixed skin harvested 1 hour or 1 day post-whole body irradiation. Radiation-induced lipid peroxidation in the skin was investigated at the same time points as the MN assay by measuring malondialdehyde (MDA) with a Thiobarbituric acid reactive substances (TBARS) assay.
  
  
  RESULTS
  None of the studied antioxidants showed significant mitigation of skin DNA damage induced by local irradiation. However, when EUK-207 or curcumin were delivered before irradiation they provided some protection against DNA damage. In contrast, all the studied antioxidants demonstrated significant mitigating and protecting effects on radiation-induced lipid peroxidation at one or more of the three time points after local skin irradiation.
  
  
  CONCLUSIONS
  Our results show no evidence for mitigation of DNA damage by the antioxidants studied in contrast to mitigation of lipid peroxidation. Since these agents have been reported to mitigate skin reactions following irradiation, the data suggest that changes in lipid peroxidation levels in skin may reflect developing skin reactions better than residual post-irradiation DNA damage in skin cells. Further direct comparison studies are required to confirm this inference from the data.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Salomeh
authors.initials: S
authors.lastname: Jelveh
authors.forename: Pavel
authors.initials: P
authors.lastname: Kaspler
authors.forename: Nirmal
authors.initials: N
authors.lastname: Bhogal
authors.forename: Javed
authors.initials: J
authors.lastname: Mahmood
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Lindsay
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
authors.forename: Susan R
authors.initials: SR
authors.lastname: Doctrow
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
mesh_terms: D000818:Animals; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D015162:Micronucleus Tests; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D008315:Malondialdehyde; D003474:Curcumin