title: From cell to man: evaluation of osteopontin as a possible biomarker of uranium exposure.
abstract: BACKGROUND
  Ore workers are conventionally monitored for exposure by measuring the uranium in their urine, but specific biomarkers of kidney damage still remain to be discovered. A recent toxicogenomics study allowed us to focus on osteopontin (OSTP) normally excreted in human urine and linked to mineral metabolism.
  
  
  OBJECTIVE
  We examined the association between osteopontin and uranium exposure both in vitro, in a human kidney cell model, and in the urine of exposed individuals.
  
  
  METHODS
  OSTP was measured in supernatants of uranium-exposed HK2 cells to establish a dose-response curve and a time course experiment. Its role was studied through a gene extinction experiment. Uranium and OSTP were then monitored in the urine of exposed nuclear fuel industry workers and a chronically exposed population. These levels were compared with those found in a non-exposed population.
  
  
  RESULTS
  The study of HK2 cells indicated that OSTP secretion decreased after uranium exposure in a concentration and time dependent manner, but its suppression does not affect cell sensitivity to uranium. In spite of wide inter-individual variability, this parameter decreases also in human urine when urinary uranium exceeds 30 μg/L after an acute exposure, a value considered to be critical for kidney damage.
  
  
  CONCLUSIONS
  This study reports how toxicogenomics can highlight putative toxicity biomarkers in an easy to access biological fluid. The decrease of urinary osteopontin in response to uranium exposure suggests kidney damage and would thus be complementary to current markers.
authors.affiliation: CEA, IBEB, SBTN, LEPC, F-30207 Bagnols-sur-Cèze, France. odette.prat@cea.fr
authors.forename: Odette
authors.initials: O
authors.lastname: Prat
authors.forename: Eric
authors.initials: E
authors.lastname: Ansoborlo
authors.forename: Nicole
authors.initials: N
authors.lastname: Sage
authors.forename: Didier
authors.initials: D
authors.lastname: Cavadore
authors.forename: Josseline
authors.initials: J
authors.lastname: Lecoix
authors.forename: Päivi
authors.initials: P
authors.lastname: Kurttio
authors.forename: Eric
authors.initials: E
authors.lastname: Quemeneur
mesh_terms: D015415:Biomarkers / Q000652:urine; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D004781:Environmental Exposure / Q000032:analysis*; D015386:Hazardous Substances / Q000633:toxicity / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008906:Mining; D053495:Osteopontin / Q000652:urine*; D014501:Uranium / Q000633:toxicity / Q000652:urine*
chemical_list: D015415:Biomarkers; D015386:Hazardous Substances; D053495:Osteopontin; D014501:Uranium