title: Fluorescence spectroscopy as a biomarker in a cell culture and in a nonhuman primate model for ovarian cancer chemopreventive agents.
abstract: OBJECTIVE
  The objective of this study was to compare the effects of chemopreventive agents on natural fluorescence emission of ovarian cells in a cell culture and in a primate model as a feasibility trial to monitor drug activity.
  
  
  METHODS
  Fluorescence emission spectra were collected from normal (NOE) and immortalized ovarian surface epithelial cells at 290, 360, and 450 nm excitation. Redox potentials were calculated and compared to % apoptosis and cell survival. Fluorescence emission spectra were collected from 18 female rhesus macaques receiving fenretinide [N-(-hydroxyphenyl)retinamide (4-HPR)] orally and/or oral contraceptive pills (OCP) or no medication. Fluorescence intensities and redox ratios were compared using a two-tailed Student's t test.
  
  
  RESULTS
  Apoptosis and cell survival correlated with fluorescence emission consistent with metabolically active proteins [flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD(P)H)] and the resulting redox ratio in cells grown with 4-HPR. The 4-HPR consistently inhibited cell survival in a dose dependent manner. Degree of correlation varied between different cell lines. In primates receiving 4-HPR, fluorescence emission was increased at 450 nm excitation, 550 nm emission consistent with FAD presence, whereas those receiving OCP showed decreased emission at 350 nm excitation, 450 nm emission consistent with decreased NAD(P)H presence. Redox ratios were increased by both drugs.
  
  
  CONCLUSIONS
  Fluorescence intensity and redox ratio appear to be altered by 4-HPR treatment in vivo and in cell culture and by OCP in vivo. Fluorescence intensity may be useful to monitor chemopreventive agents in clinical trials.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. mbrewer@azcc.arizona.edu
authors.forename: Molly
authors.initials: M
authors.lastname: Brewer
authors.forename: Urs
authors.initials: U
authors.lastname: Utzinger
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: E Neely
authors.initials: EN
authors.lastname: Atkinson
authors.forename: William
authors.initials: W
authors.lastname: Satterfield
authors.forename: Nelly
authors.initials: N
authors.lastname: Auersperg
authors.forename: Rebecca
authors.initials: R
authors.lastname: Richards-Kortum
authors.forename: Michele
authors.initials: M
authors.lastname: Follen
authors.forename: Robert
authors.initials: R
authors.lastname: Bast
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003276:Contraceptives, Oral / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005240:Feasibility Studies; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D008253:Macaca mulatta; D009249:NADP / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000517:prevention & control*; D010053:Ovary / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010084:Oxidation-Reduction / Q000187:drug effects; D012016:Reference Values; D013050:Spectrometry, Fluorescence
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D003276:Contraceptives, Oral; D005182:Flavin-Adenine Dinucleotide; D017313:Fenretinide; D009249:NADP