Limb deformity induced in chick embryo by hydroxyurea.
After a dose of 800 micrograms of hydroxyurea (HU) was administered to day-4 chick embryos in ovo, the limb deformity including micromelia was observed. We examined the teratogenic mechanism of the action for HU by using histochemical and biochemical techniques. The present study provides histological evidence for the cell death and the depression of cell proliferation just after the treatment with HU and the retardation in periosteal ossification during the process of repair and/or recovery from cell death. On the other hand, the incorporation of [3H]glucosamine and [35S]sulfate into glycosaminoglycan was inhibited at day-7 and day-9, when the embryos are in the process of repair and/or recovery. The cartilage specific proteoglycan, an index of chondrogenesis, appeared at day-7, but the ratio of cartilagenous proteoglycan/noncartilagenous proteoglycan in the treated limbs was depressed. These results suggest that the slight retardation in chondrogenesis and/or the incomplete function of chondrocyte were induced by the treatment with HU in chick embryos. It is considered from above observation that the retardation in chondrogenesis and osteogenesis caused during the repair and/or recovery process of cell death brought about the limb deformity; shortening, thinning and bending of hind limbs.
D000818:Animals; D002642:Chick Embryo; D004247:DNA / Q000096:biosynthesis; D006025:Glycosaminoglycans / Q000378:metabolism; D006918:Hydroxyurea / Q000633:toxicity*; D017880:Limb Deformities, Congenital; D011509:Proteoglycans / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013723:Teratogens; D013997:Time Factors; D014574:Uronic Acids / Q000378:metabolism
D006025:Glycosaminoglycans; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; D013723:Teratogens; D014574:Uronic Acids; D004247:DNA; D006918:Hydroxyurea