title: Urinary biomarkers of oxidative status in a clinical model of oxidative assault.
abstract: BACKGROUND
  We used doxorubicin-based chemotherapy as a clinical model of oxidative assault in humans.
  
  
  METHODS
  The study recruited newly diagnosed breast cancer patients (n = 23). Urine samples were collected immediately before (T0) and at 1 hour (T1) and 24 hours (T24) after i.v. administration of treatment. Measurements included allantoin and the isoprostanes iPF(2alpha)-III, iPF(2alpha)-VI, and 8,12-iso-iPF(2alpha)-VI along with the prostaglandin 2,3-dinor-iPF(2alpha)-III, a metabolite of iPF(2alpha)-III. All biomarkers were quantified using liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  In all subjects, the levels of the biomarkers increased at T1: allantoin by 22% (P = 0.06), iPF(2alpha)-III by 62% (P < 0.05), iPF(2alpha)-VI by 41% (P < 0.05), 8,12-iso-iPF(2alpha)-VI by 58% (P < 0.05), and 2,3-dinor-iPF(2alpha)-III by 52% (P < 0.05). At T24, the F2-isoprostanes returned to their baseline levels; the levels of allantoin continued to increase, although the T24-T0 difference was not statistically significant.
  
  
  CONCLUSIONS
  These results indicate that urinary F2-isoprostanes are valid biomarkers and allantoin is a promising biomarker of oxidative status in humans.
  
  
  CONCLUSIONS
  The levels of biomarkers change quickly in response to oxidative assault and can be used to monitor oxidative status in humans in response to treatments related either to generation of free radicals (chemotherapy and radiation therapy) or to antioxidants (inborn metabolic diseases and Down syndrome).
authors.affiliation: Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC 27710, USA. dora.ilyasova@duke.edu
authors.forename: Dora
authors.initials: D
authors.lastname: Il'yasova
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Frances
authors.initials: F
authors.lastname: Wang
authors.forename: Adviye A
authors.initials: AA
authors.lastname: Tolun
authors.forename: Karel
authors.initials: K
authors.lastname: Base
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Young
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Marks
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mixon
authors.forename: Richard
authors.initials: R
authors.lastname: DiGiulio
authors.forename: David S
authors.initials: DS
authors.lastname: Millington
mesh_terms: D000293:Adolescent; D000328:Adult; D000481:Allantoin / Q000652:urine; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000652:urine*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000652:urine*; D002853:Chromatography, Liquid; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D028441:F2-Isoprostanes / Q000652:urine*; D005260:Female; D005609:Free Radicals / Q000652:urine; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D018384:Oxidative Stress; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D028441:F2-Isoprostanes; D005609:Free Radicals; D000481:Allantoin; D004317:Doxorubicin; D003520:Cyclophosphamide