Cardiovascular malformations induced by bromodeoxyuridine in the chick embryo.
For the study of morphogenesis and early embryonic development, 5-bromodeoxyuridine (BUdR), a halogenated analogue of thymidine, is incorporated into replicating DNA and serves as a valuable tool. To study the teratogenicity of BUdR on the developing chick cardiovascular system, we topically administered graded doses of BUdR (32.6-325.6 nmol) in ovo during Hamburger-Hamilton stages 15 to 16. We also administered to a parallel group of embryos corresponding nanomole doses of thymidine during identical stages of development. In the thymidine-treated group, survival rates and cardiovascular anomaly rates did not differ statistically from those in the chick Ringer's control group. Both survival rates and cardiovascular anomaly rates in the BudR-treated group were dose-responsive. Among 78 embryos with cardiovascular anomalies induced by BUdR, vascular malformations were found in 96%. These anomalies included interruption of the right fourth aortic arch, absence or hypoplasia of the right and/or left sixth aortic arch, and persistence of the left fourth aortic arch. Interruption of the right fourth aortic arch was always associated with intracardiac anomalies. Intracardiac anomalies were found in 54% of the embryos; these included ventricular septal defect, double outlet right ventricle, and persistent truncus arteriosus. Subclavian artery malformations were noted in 95% of the embryos. Possible mechanisms for BUdR-induced malformations in the cardiovascular system of the chick are discussed.
Nishibatake
M
M
Department of Pathology, University of Wisconsin Medical School, Madison 53792.
Kargas
S A
SA
Bruyere
H J
HJ
Gilbert
E F
EF
D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities; D001973:Bromodeoxyuridine / Q000633:toxicity*; D002642:Chick Embryo; D006330:Heart Defects, Congenital / Q000139:chemically induced*; D006820:Hyaluronic Acid / Q000096:biosynthesis; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects; D013348:Subclavian Artery / Q000002:abnormalities; D013723:Teratogens
D013723:Teratogens; D006820:Hyaluronic Acid; D001973:Bromodeoxyuridine