The gene expression of CYP 3A is modify according to the duration of DU-exposure
A time-lapse uranium contamination study was developed in order to assess changes in this detoxification system over a period ranging from sub-chronic exposure (1 month) to long-term exposure (18 months).
The results show a modify response in the gene expression of CYP3A according to the duration of exposure to DU. No change in gene expression was observed after 1, 3 and 18 months of exposure. After 6 months’ exposure, the gene expression was decreased whereas it was increased after 9 months. These variations over time suggest that adaptation or compensation phenomena probably occur in the body and tissue resulting in a variation in the level of expression of xenobiotic metabolizing enzymes. Moreover, previous study showed that the accumulation of uranium in the tissues in not gradual as a function of time and does not lead to a steady state [Paquet et al. 2006]. The biological variations observed can therefore depend on the concentration of uranium present in the tissues. In fact, more significant effects are observed after 9 months’ contamination – the time during which uranium was present in larger quantities in the liver.
These results corroborate earlier data showing that CYP3A, one of the major xenobiotic metabolizin enzymes, is targeted by uranium.