Pregnant rats received the lathyrogen beta-aminopropionitrile (1,500 mg/kg) intraperitoneally on day 16 (plug day = 0 day). Kyphoscoliosis was produced in a high incidence in the fetuses at the level of the upper thoracic spine as early as 24 hours after treatment. Although most of the affected newborns died within two weeks, survivors were studied until 20 weeks after birth. Survivors developed paraplegia in consequence of kyphoscoliosis. Both spinal deformity and motor disturbance were progressive. Biochemical and electron microscopic observations suggested that beta-aminopropionitrile treatment resulted in an inhibition of collagen formation in the spinal column and surrounding longitudinal ligaments of the fetuses six hours after the treatment. In addition, electron micrographs of vertebral bodies showed a decrease of proteoglycan granules in the extracellular matrix. Therefore, rupture and collapse of weakened ligaments and vertebral bodies might result in severe spinal deformity and spinal cord lesion.
Abnormalities, Drug-Induced Aminopropionitrile