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 micrograms/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 micrograms/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 micrograms/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 micrograms/ml of ETU. The concentrations of ETU that inhibited the production of differentiated foci by 50% (IC50) were 170 micrograms/ml in LB cells of day 11, and greater than 600 micrograms/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.
Tsuchiya
T
T
Division of Medical Chemistry, National Institute of Hygienic Sciences, Tokyo, Japan.
Takahashi
A
A
Asada
S
S
Takakubo
F
F
Ohsumi-Yamashita
N
N
Eto
K
K
D000015:Abnormalities, Multiple / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005031:Ethylenethiourea / Q000633:toxicity*; D005865:Gestational Age; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens / Q000633:toxicity
D013723:Teratogens; D005031:Ethylenethiourea