THE EFFECTS OF SODIUM SELENITE AND SELENOMETHIONINE ON MURINE LIMB DEVELOPMENT IN CULTURE

Excessive selenium in the environment causes perturbed embryonic devel opment in birds; however, excessive selenium in mammals has not been s hown to cause similar maldevelopment. The present study was performed to determine whether the lack of selenium-induced limb defects in mamm als is due to either differences in pharmacokinetics or tissue sensiti vity to the compound, or both. Sodium selenite (SS) and selenomethioni ne (SM) were added to BGJb medium containing 20% fetal bovine serum, i n which limbs from CD-1 mouse embryos taken 12 d following conception were cultured. Concentrations of SS and SM ranged from 2 to 20 times t he level of selenium normally present in fetal bovine serum (0.2, 0.6, 1.0, 2.0, or 4.0 mug/ml). Limbs were grown for 72 h, fixed, stained w ith Alcian blue GX to highlight cartilage anlagen, and analyzed to det ermine tissue and anlage areas and shape factors. Sodium selenite indu ced a concentration-response maldevelopment of ulnar, radius, and hume rus anlagen and delayed development of phalanges, whereas SM did not. Changes in development became obvious at SS levels four times normal ( 0.6 mug/ml). The size and length of anlagen also decreased (p < 0.0001 ). At six times the concentration of SS (1.0 mug/ml), areas occupied b y cartilage anlagen were decreased 20-fold, with virtually no chondrog enesis evident in phalanges at higher concentrations. The results of t hese studies indicate that SS can cause deficits in early mammalian li mb development if the element is allowed to reach the developing tissu e, whereas the SM does not. We conclude that tissue differences in res ponse and placental transfer may account for the differences seen amon g species.