Production élective de la phocomélie sous l’influence d’ypérite azotée

Abstract

ABSTRACT Chick embryos of to days of age (Stages 17-22 of Hamilton & Hamburger) were injected with nitrogen mustard (methyl-bis-chlorethylamine) dissolved in distilled water. Each embryo received a dose of from 0 · 6 to 1 · 6 μg. Most of the embryos (181 out of 199) showed serious malformations of the limbs of which the most characteristic was phocomelia. Embryos which died, or were sacrificed, before 10 days of age had very short limbs most of which in course of degenerating. Embryos taken at ages greater than 12 days showed various degrees of alterations of wings and legs. In the most severe cases the digits appeared to be inserted directly into the flank of the animal (type I). The least affected cases showed feet or wings shortened and deformed (type III). Between these two types are placed a group whose members approach the phocomélie type but in whom a short segment separates the distal parts of the limb from the body (type II). The digits were also malformed, and both fusions (syndactyly) and regression was observed. There were very few other malformations. There were many aberrations in the development of the skeletal elements. In the foot, the fibula was first to disappear. In the wing, the ulna or the radius was affected. The other elements were generally reduced in size or abnormally developed. Fusions and abnormal bends were seen. The femur and the humerus were generally altered less than the other intermediate pieces of the skeleton. This work brings evidence of a selective action of nitrogen mustard in the limb rudiments. Certain parts of these rudiments are more sensitive than others. Certain elements of the skeleton disappear in a constant order: fibula (foot), radius or ulna (wing), digit I of the foot. The most typical malformation obtained was phocomelia, seen in 65 out of 107 cases. The distal structures, the digits, are least affected. The hypothesis of a selective action upon mesodermal structures is put forward. Other malformations were rare, 26 out of 107 autopsied before the 12th day of incubation showed scoliosis of the neck. Among them, four showed a malformation of the eye.