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Selenite and Selenate Inhibit Human Lymphocyte Growth via Different Mechanisms¹

The Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm [G. S., M. B., A. H.]; Department of Bioscience, Center for Biotechnology, Karolinska Institutet, Novum. S-141 57 Huddinge [G. S.]; and Department of Medical Radiobiology, Karolinska Institutet, S-171 76 Stockholm [S. S.], Sweden

Selenium compounds like selenite and selenate have strong inhibitory effects, particularly on mammalian tumor cell growth by unknown mechanisms. We found that the addition of sodium selenite and sodium selenate inhibited the growth of human 3B6 and BL41 lymphocytes. Selenite was more potent because 10 µM selenite produced a growth inhibitory effect similar to that of 250 µM selenate. The mechanism of action of selenite and selenate appears to be different. 3B6 and BL41 cells treated with selenite accumulated in the S-phase; however, selenate caused an accumulation of cells in G₂. Selenite-mediated growth inhibition was irreversible, although the effects of selenate could be reversed. Selenite, in contrast to selenate, is efficiently reduced by the thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH). At concentrations required to observe a similar effect on cell growth, the activity of thioredoxin reductase, recently shown to be a selenoprotein, increased in selenite-treated cells and decreased in selenate-treated cells. Ribonucleotide reductase activity was inhibited in an in vitro assay by selenite and selenodiglutathione but not by selenate. These results show that selenite and selenate use different mechanisms to inhibit cell growth.

¹ This work was supported by grants from the Swedish Medical Research Council (Projects 13X-10370, 13P-10636, and 13X-3529), the Swedish Cancer Society (961), and the Karolinska Institute.

² To whom requests for reprints should be addressed, at Department of Bioscience, Center for Biotechnology, Karolinska Institutet, Novum, S-141 57 Huddinge, Sweden. Phone: 46-8-608-91-62; Fax: 46-8-74-55-38; E-mail: Giannis.Spyrou@mbb.ki.se.

Received 2/12/96. Accepted 8/ 1/96.

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