Stichting Laka

Publicatie Laka-bibliotheek:
In vivo effects of chronic contamination with depleted uranium on CYP3A and associated nuclear receptors PXR and CAR in rat (2005)

AuteurSouidi, Guegen, Linard
6-05-0-00-29.pdf
Datumjuni 2005
Classificatie 6.05.0.00/29 (VERARMD URANIUM - ALGEMEEN (oa. Gezondheidsonderzoek))
Voorkant

Uit de publicatie:

                                                  Toxicology xxx (2005) xxx–xxx




                  In vivo effects of chronic contamination with
               depleted uranium on CYP3A and associated nuclear
                        receptors PXR and CAR in the rat
         M. Souidi ∗ , Y. Gueguen, C. Linard, N. Dudoignon, S. Grison, C. Baudelin,
                 C. Marquette, P. Gourmelon, J. Aigueperse, I. Dublineau
          Institut de Radioprotection et de Sˆuret´e Nucl´eaire, Direction de la RadioProtection de l’Homme, Service de Radiobiologie
    et d’Epid´emiologie, Laboratoire de Radiotoxicologie Exp´erimentale, IRSN, B.P. No. 17, F 92262 Fontenay-aux-Roses Cedex, France

                           Received 8 April 2005; received in revised form 10 June 2005; accepted 13 June 2005




Abstract

   In addition to its natural presence at high concentrations in some areas, uranium has several civilian and military applications
that could cause contamination of human populations, mainly through chronic ingestion. Reports describe the accumulation
of this radionuclide in some organs (including the bone, kidney, and liver) after acute or chronic contamination and show that
it produces chemical or radiological toxicity or both. The literature is essentially devoid of information about uranium-related
cellular and molecular effects on metabolic functions such as xenobiotic detoxification. The present study thus evaluated rats
chronically exposed to depleted uranium in their drinking water (1 mg/(rat day)) for 9 months. Our specific aim was to evaluate
the hepatic and extrahepatic mRNA expression of CYP3A1/A2, CYP2B1, and CYP1A1 as well as of the nuclear receptors PXR,
CAR, and RXR in these rats.
   CYP3A1 mRNA expression was significantly higher in the brain (200%), liver (300%), and kidneys (900%) of exposed rats
compared with control rats, while CYP3A2 mRNA levels were higher in the lungs (300%) and liver (200%), and CYP2B1
mRNA expression in the kidneys (300%). Expression of