title: Contrasting roles of dietary selenium and selenoproteins in chemically induced hepatocarcinogenesis.
abstract: 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 (Trsp (A37G) 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 Trsp (A37G) 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 Trsp A37G 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.
authors: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Marina V
authors: MV
authors: Kasaikina
authors: Anton A
authors: AA
authors: Turanov
authors: Andrei
authors: A
authors: Avanesov
authors: Ulrich
authors: U
authors: Schweizer
authors: Sandra
authors: S
authors: Seeher
authors: Roderick T
authors: RT
authors: Bronson
authors: Sergey N
authors: SN
authors: Novoselov
authors: Bradley A
authors: BA
authors: Carlson
authors: Dolph L
authors: DL
authors: Hatfield
authors: Vadim N
authors: VN
authors: Gladyshev
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D004032:Diet; D005260:Female; D005838:Genotype; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics; D012643:Selenium / Q000008:administration & dosage*; D051140:Selenoproteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012345:RNA, Transfer, Amino Acid-Specific; D051140:Selenoproteins; C036928:tRNA, selenocysteine-; D012643:Selenium
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