Publicatie Laka-bibliotheek:
In vivo effects of chronic contamination with depleted uranium on CYP3A and associated nuclear receptors PXR and CAR in rat
Auteur | Souidi, Guegen, Linard |
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6-05-0-00-29.pdf |
Datum | juni 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