Selenium has
cancer protective effects in a variety of experimental systems. Currently, it is not known whether
selenoproteins or low molecular weight selenocompounds are responsible for this activity. To evaluate the contribution of
selenoproteins to the
cancer protective effects of
selenium, we used transgenic mice that carry a mutant
selenocysteine transfer RNA gene, which causes reduced
selenoprotein synthesis.
Selenium homeostasis was characterized in liver and colon of wild-type and transgenic mice fed
selenium-deficient diets supplemented with 0, 0.1, or 2.0 microg
selenium (as
selenite)/g diet. (75)Se-labeling, Western blot analysis, and enzymatic activities revealed that transgenic mice have reduced (P < 0.05) liver and colon
glutathione peroxidase expression, but conserved
thioredoxin reductase expression compared with wild-type mice, regardless of
selenium status. Transgenic mice had more (P < 0.05)
selenium in the nonprotein fraction of the liver and colon than wild-type mice, indicating a greater amount of low molecular weight selenocompounds. Compared with wild-type mice, transgenic mice had more (P < 0.05)
azoxymethane-induced aberrant crypt formation (a preneoplastic lesion for
colon cancer). Supplemental
selenium decreased (P < 0.05) the number of aberrant crypts and
aberrant crypt foci in both wild-type and transgenic mice. These results provide evidence that a lack of
selenoprotein activity increases
colon cancer susceptibility. Furthermore, low molecular weight selenocompounds reduced preneoplastic lesions independent of the
selenoprotein genotype. These results are, to our knowledge, the first to provide evidence that both
selenoproteins and low molecular weight selenocompounds are important for the
cancer-protective effects of
selenium.