|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1998 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1997 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Bis-diamine administration to pregnant rats induces conotruncal anomalies.
To know teratologic effects of bis-diamine depending on the developmental stage, we examined neonates and embryos from Wister mother rats to which a single dose of 200 mg his-diamine was administered at 10, 11, or 12 days of gestation (group 1, 2, and 3, respectively). The neonates from group 1 (n 86) had aortjc arch anomalies in 100 %, and those from group 2 (n = 95) and 3 (n = 108) had aortic arch anomalies and truncus arteriosus communis in 92.8%, and aortic arch anomalies and tetralogy of Fallot in 45.4%, respectively. In order to examine the early morphological effects of bis-diamine, we cultured four embryos from each group for 24 hours following the procedures described by Cockroft and New (1978). The embryos from group 1 showed delayed closure of the neural tube and immature cardiac looping with undifferentiated third, fourth, and sixth Nortek arches. Immunohistological study using anti-N-CAM antibody revealed that N-CAM positive cells were sparsely distributed around the neural tube. The embryos from group 2 had an enlarged and dilated ventricle and winding and elongate outflow tract in which regurgitant blood flow was observed, whereas none in controls. Furthermore, two of the embryos had a partial pericardial defect. A continuous N-CAM immunopositive chain from the neural tube to the heart was clearly seen, though thin when compared with controls. No morphological and circulatory difference was seen between embryos from group 3 and controls.
These results suggested that bis-diamine may disturb normal development and migration of cardiac neural crest or mesenchymal cells to induce various cardiovascular anomalies depending on the developmental stage.