Effects of chronic contamination through ingestion of 137CS on hepatic cholesterol metabolism in adult rats

Titre du congrès :15th International Conference on Cytochrome P450 Ville du congrès :Bled Date du congrès :17/06/2007

Background: Chernobyl nuclear accident in 1986 fallout lead to the dispersion of many radionuclides in the environment, 137Caesium (137Cs) which accumulated in the ground. Because 137Cs has a long half-life (30 years), populations living on contaminated areas have since then been exposed to a low dose contamination through food ingestion. Our aim is to address the public health issue raised by the long-term staying of these populations on contaminated areas. In this study, we mimicked this pattern of contamination by feeding rats drinking water with 137Cs at a post-accidental level (150 Bq/rat/day) during 9 months. We then studied the potential harmful and/or side effects of this chronic low-dose contamination on hepatic cholesterol metabolism. Results: The plasma lipid pattern was unchanged in contaminated rats, but the plasma levels of total bilirubin and glucose were increased (251%, p=0.006 and 20%, p=0.049 respectively). None of the CYP 450 we studied showed any variation in gene expression (CYP27A1, CYP7A1, CYP7B1, CYP8B1, CYP51) or in specific activity (CYP27A1, CYP7A1). However, some of the nuclear receptors involved in their regulation did exhibit some changes. Gene expression of LXRα decreased (27%, p = 0.028) and that of RXR followed an increasing trend (37%, p=0.053). Besides, ACAT 2 expression decreased (44%, p = 0.05). Conclusion: These results clearly show that the global cholesterol metabolism is not disrupted by a chronic low-dose contamination through ingestion of 137Cs. Main CYP450 do not undergo any changes, but several molecular modifications are seen, notably in nuclear receptors of prime importance in cholesterol and glucose metabolisms. Although this leads to no physiopathological outcome, it is of interest to extend the scope of our investigations to more sensitive models: growing pups and organisms predisposed to hypercholesterolemia.