COMPARATIVE-STUDIES OF EMBRYOTOXIC ACTION OF ETHYLENETHIOUREA IN RAT WHOLE EMBRYO AND EMBRYONIC-CELL CULTURE

The effects of ethylenethiourea (ETU) were investigated using rat (Wistar-imamichi) embryos cultured from days 11 to 13 of gestation or cultured rat embryonic cells extracted on day 11. Malformations in cultured embryos at the concentration of 30-mu-g/ml of ETU were found in the head and tail, which were severely affected, as well as the limb and face. All embryos exposed to 150 and 300-mu-g/ml of ETU had malformed heads, tails, limbs, and facial configurations. Protein contents of the cultured embryos were decreased dose-dependently at the concentrations ranging from 30 to 300-mu-g/ml. In the histological studies of the cultured embryos with ETU, thinner neuroepithelium in head was observed. In the embryonic cells extracted on day 11 of gestation, ETU dose-dependently inhibited the differentiation of midbrain (MB) cells into neurons and that of limb bud (LB) cells into chondrocytes at the concentrations ranging from 30 to 600-mu-g/ml of ETU. The concentrations of ETU that inhibited the production of differentiated foci by 50% (IC50) were 170-mu-g/ml in LB cells of day 11, and > 600-mu-g/ml in LB cells on day 12 of development. Therefore, differentiation of MB cells was more sensitive to ETU than the differentiation of LB cells. These results indicated that there was a reasonable correlation of ETU induced changes in cultured whole embryos and embryonic cells.