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Effects of chronic contamination with depleted uranium on xenobiotic biotransformation enzymes in the rat



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Gueguen Y., Paquet F., Voisin P. and Souidi M., 14th International conference on .-cytochromes P450, Biochemistry, Biophysics and Bioinformatics, Dallas, Texas (USA), -pp 61-65, Medimond, International Proceedings.


Xenobiotic metabolizing enzymes play a central role in the metabolism and/or detoxification of foreign compounds such as drugs. Few studies examined the biological effect of uranium, a radionuclide present in the environment as a result of natural deposits and its extensive use in nuclear industry and military applications. This study evaluated the effects of low dose of depleted uranium (DU, drinking water) on the gene expression of xenobiotic biotransformation enzyme in rats: CYP3A, 2B1, 2C11 and PXR were up-regulated in the liver and the kidney of DU-treated rats compared to control animals. No modifications were observed on mRNA levels of some xenobiotic-metabolizing phase II enzymes and ABC transporters. The stimulating effect of DU on these specific CYPs could lead to hepatic and/or renal toxicities in the setting of drug administration.