title: Chronic exposure to natural uranium via drinking water affects bone in growing rats.
abstract: BACKGROUND
  Bone is the main site of uranium accumulation after long term contamination. Several studies describe that at high dose of exposure, uranium impairs bone growth. Nevertheless little is known about the effects of chronic exposure at low doses of this radionuclide on bone, especially when ingested via drinking water, which is considered as the main exposure pathway for the public.
  
  
  METHODS
  In this study, male rats were exposed to natural uranium in drinking water for a 9 month period, either at 40 mg l(-1) starting just after birth (post-natal model) or starting at 3 months of age (adult model).
  
  
  RESULTS
  In the post-natal model at 40 mg l(-1), three-dimensional microtomography analysis showed that NU decreased significantly the cortical bone diameter in NU-contaminated rats. Bone histomorphometry analysis also showed a significant increase of the osteoid thickness in trabecular bone of the femur of NU-contaminated rats. In addition, mRNA expression in trabecular bone of genes involved in osteoblast differentiation (OSX, BMP2, RUNX2), bone remodeling (TRAP, OCN), bone mineralization (BSP, OPN, DMP1), calcium transport (TRPV5) as well as vitamin D receptor (VDR) was significantly decreased in this model. In contrast, in the adult model, no morphometric, cellular and molecular changes were observed in bone.
  
  
  CONCLUSIONS
  This study showed for the first time that NU at this concentration has no detectable effect in adult bone while it significantly affects growing bone, which thus appears more sensitive to low dose contamination by this radionuclide.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), DRPH, SRBE, LRTOX, BP 17, F-92262 Fontenay-aux-Roses Cedex, France. marieme.wade-gueye@irsn.fr
authors.forename: Ndéye Marième
authors.initials: NM
authors.lastname: Wade-Gueye
authors.forename: Olivia
authors.initials: O
authors.lastname: Delissen
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Aigueperse
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dublineau
authors.forename: Maâmar
authors.initials: M
authors.lastname: Souidi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001846:Bone Development / Q000187:drug effects* / Q000235:genetics*; D001842:Bone and Bones / Q000187:drug effects*; D060766:Drinking Water; D005269:Femur / Q000187:drug effects*; D020869:Gene Expression Profiling; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014501:Uranium / Q000633:toxicity*
chemical_list: D060766:Drinking Water; D012333:RNA, Messenger; D014501:Uranium