Thiosemicarbazide-induced osteolathyrism in metamorphosing Xenopus laevis.

Exposure of Xenopus laevis tadpoles to thiosemicarbazide (TSC), at concentrations from 10 to 75 mg/liter, causes an inhibition of metamorphosis and produces the classic manifestations of the experimental disease, osteolathyrism. Concentration-dependent effects of TSC exposure are observed in growth rate and in the severity of the osteolathyrogenic effect. Concentrations allowing the most rapid growth produce the more extreme osteolathyrogenic defects. Osteolathyrism in these animals is identical in characteristics to the condition described in a wide variety of vertebrate species. In Xenopus, osteolathyrism is expressed morphologically as anomalies in bone development, skeletal conformation, and abnormal connective tissue organization in the aorta wall. The underlying defect responsible for these observations is apparently a perturbation of collagen fiber formation and maturation, as evidenced ultrastructurally by aberrant distribution and packing of collagen fibers. It is suspected that TSC produces this effect by altering the availability of copper ion, a cofactor to lysyl oxidase, an essential enzyme for intermolecular cross-linking of procollagen. This step in collagen metabolism has been consistently implicated as the site of action of several osteolathyrogenic agents. Xenopus tadpoles present a classic response to this known osteolathyrogen and demonstrate a high degree of uniformity of response within the experimental groups. In view of the developmentally significant events accessible with this system and inherent logistic and economical advantages, the metamorphosing tadpole of Xenopus holds considerable potential for the experimental analysis of teratogenic agents and events.