Nimustine hydrochloride (
ACNU) is a nitrosourea derivative
anticancer agent which has been shown to cause
persistent truncus arteriosus in chick embryos. The objective of this study was to confirm the teratogenic effects of
ACNU on the cardiovascular system of chick embryos and to determine whether
ACNU induces
persistent truncus arteriosus by interfering with neural crest cells. Various doses of
ACNU ranging from 10 to 200 micrograms were injected under the chorioallantoic membrane of chick embryos on the third day of incubation.
Saline solution was used as the control. After 10 to 11 days of incubation, 242 (46%) survivors of the 524 treated eggs were obtained. The survival rates of the embryos and the frequencies of cardiovascular anomalies were dose dependent. Of 146 embryos with cardiovascular anomalies, 104 (71%) had
persistent truncus arteriosus.
Ventricular septal defect and
double-outlet right ventricle were seen in 37 (25%) and one (1%), respectively. Aortic arch anomalies were seen in 116 embryos (79%). Quail-chick chimeras (chick embryos with quail cardiac neural crest) were treated with 50 micrograms of
ACNU and examined histologically 24 hours later. These chimeras showed dying neural crest cells in the pharyngeal arches. Dying cells were also noted in the neural tube, cranial ganglia, retina, and otocyst. These results suggest that
persistent truncus arteriosus in chick embryos treated with
ACNU is induced by neural crest cell death.