Inhibition of amino acid incorporation in a cell-free system and inhibition of protein synthesis in cultured cells by reaction products of selenite and thiols.
Reaction products of selenite with thiols were tested for an inhibitory effect on amino acid incorporation in a cell-free system derived from rat liver and on protein synthesis in intact P815 and L1210 cells. In the cell-free system maximum inhibition, up to 96%, was reached at about 10 microM selenium. In intact cells inhibitory effect varied depending on which reaction product or cell line was used. Maximum inhibition was obtained after 30 min of incubation with selenium concentrations ranging from 0.25 microM to over 7 microM. Selenite itself also inhibited protein synthesis of L1210 cells, but only after 90 min of incubation and starting at selenium concentrations of 2 microM. Inhibition of protein synthesis in intact cells was followed by cell death. Pre-incubation of the reaction products of a monothiol (2-propanethiol) and of a vicinal dithiol (2,3-dimercapto-1-propanol) in culture medium showed a rapid decrease of the inhibitory capability of the product from the monothiol, but not of the product from the dithiol. The results indicate that selenite and a thiol react to form products which have differential toxic effects to cells in vitro.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D012515:Mast-Cell Sarcoma / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011506:Proteins / Q000235:genetics*; D012513:Sarcoma, Experimental / Q000378:metabolism; D020887:Selenious Acid; D012643:Selenium / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D000596:Amino Acids; D009363:Neoplasm Proteins; D011506:Proteins; D013438:Sulfhydryl Compounds; D020887:Selenious Acid; D012643:Selenium