Contrasting roles of dietary selenium and selenoproteins in chemically induced hepatocarcinogenesis
Menée à l'aide d'un modèle murin présentant une mutation du gène codant pour l'ARN de transfert de la sélénocystéine, cette étude analyse le rôle des sélénoprotéines et des composés séléniques dans la prévention de la carcinogenèse du foie induite par la diéthylnitrosamine
Selenium (Se) has long been known for its cancer prevention properties, but the molecular basis remains unclear. The principal questions in assessing the effect of dietary Se in cancer are whether selenoproteins, small molecule selenocompounds, or both, are involved, and under which conditions and genotypes Se may be protective. In this study, we examined diethylnitrosamine-induced hepatocarcinogenesis in mice lacking a subset of selenoproteins due to expression of a mutant selenocysteine tRNA gene (TrspA37G mice). To uncouple the effects of selenocompounds and selenoproteins, these animals were examined at several levels of dietary Se. Our analysis revealed that tumorigenesis in TrspA37G mice maintained on the adequate Se diet was increased. However, in the control, wild-type mice, both Se deficiency and high Se levels protected against tumorigenesis. We further found that the Se-deficient diet induced severe neurological phenotypes in TrspA37G mice. Surprisingly, a similar phenotype could be induced in these mice at high dietary Se intake. Overall, our results show a complex role of Se in chemically induced hepatocarcinogenesis, which involves interaction among selenoproteins, selenocompounds and toxins, and depends on genotype and background of the animals.
http://carcin.oxfordjournals.org/content/early/2013/02/05/carcin.bgt011.abstract