Contrasting roles of dietary selenium and selenoproteins in chemically induced hepatocarcinogenesis

Carcinogenesis. 2013 May;34(5):1089-95. doi: 10.1093/carcin/bgt011. Epub 2013 Feb 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / chemically induced*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Diet
  • Female
  • Genotype
  • Liver Neoplasms / chemically induced*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • RNA, Transfer, Amino Acid-Specific / genetics
  • Selenium / administration & dosage*
  • Selenoproteins / genetics*
  • Selenoproteins / metabolism*


  • RNA, Transfer, Amino Acid-Specific
  • Selenoproteins
  • tRNA, selenocysteine-
  • Selenium