References and definitions
1 : Caroline Rouas carried out her research studies at IRSN. She submitted her thesis on 01 October 2010 on sur l'étude des mécanismes mis en jeu lors d’une exposition à l’uranium appauvri sur le système de détoxification in vivo et in vitro (study of the mechanisms involved on exposing in-vivo and in-vitro drug metabolism to uranium).
2 : A xenobiotic is a generally hydrophobic compound. The liver is the main organ involved in their metabolism and elimination. To do this, it is composed with three groups of proteins. Phase I enzymes, the so-called functionalisation enzymes, in which P450 cytochromes (CYP) play a major role, are located on the surface of the endoplasmic reticulum. The active site of the CYP contains an iron (Fe) atom surrounded by nitrogen atoms (N). The organic compound is oxidised and a molecular oxygen atom is incorporated into the chemical product (-OH). The main phase II enzymes, the so-called conjugating enzymes, are divided into three sub-groups: Glutathion S transferases (GST), UDPglucuronosyl transferases (UGT) and sulfotransferases (SULT). They are involved in transforming the compound by adding a hydrophilic compound. The phase III transporters (MDR: multi drug resistance protein, MRP: multi drug resistance-associated protein) aim to eliminate the compound which is rendered water-soluble, outside the cell, towards the blood system in order for it to be eliminated in the urine through the kidneys.
Gueguen, Y.,Mouzat K.,Ferrari L.,Tissandie E.,Lobaccaro J. M.,Batt A. M.,Paquet F.,Voisin P.,Aigueperse J.,Gourmelon P.and Souidi M. (2006b) [Cytochromes P450: xenobiotic metabolism, regulation and clinical importance]. Ann Biol Clin (Paris) 64, 535-48 Moore, M. R. (2004) A commentary on the impacts of metals and metalloids in the environment upon the metabolism of drugs and chemicals. Toxicol Lett 148, 153-8