[Patterns of effects of triethylenemelamine (TEM) and their treatment-phase specifity during organogenesis of the chick embryo : I. Changes in the dimensions of the body, the outer form and surface structures].

Chick embryos were treated with the cytostatic substance triethylenemelamine (TEM) on the 3 1/2th, 4th or 4 1/2th day of incubation (one injection per egg). One group of embryos was fixed in Bouin's solution on the 7th or between the 9th and 11th day of incubation for the comparative study of alterations of the external morphology. The majority of embryos was investigated for alterations in the cartilaginous skeleton after staining with methylene blue and subsequent clearing.This paper deals with the experimental technique, a general survey of the experimental material and the results obtained from the Bouin-fixed embryos. The analysis of the cartilaginous skeleton will be subject of later publications (parts II and III).The teratogenic dose of 7 μg TEM (administration into the air chamber, = "standard treatment", fixation between 9th and 11th day) was-under the given experimental conditions - equivalent to the embryonal LD 50 when the treatment occurred on the 4th day. For the various stages of treatment (standard treatment at the 3 1/2th, 4th or 4 1/2th day, then fixation between 9th and 11th day of incubation) lethality decreases with increasing age of treatment. Injection of TEM into the yolk sac results in more marked malformations than does injection of the same dose into the air chamber. Treatment with 6-10 μg TEM (injection into the air chamber) or with 5-7 μg TEM (injection into the yolk sac) led to reduction of all dimensions of the body in all experimental embryos (including those with normal outer appearance). In general, the body dimensions were more markedly reduced, the more malformed an embryo was. After standard treatment of the three experimental stages and fixation on the 7th day of incubation the lengths of the head, of the trunk and of the hind legs respectively were more reduced, the earlier the treatment occurred.The outer malformations characteristic for the present experimental material are the following: oedema in various forms, enlarged and anteriorly transposed umbilicus, umbilical hernia, bending, torsion and reduction of extremities (in most cases combined with oligodactylism), reduction and bending downwards of the upper beak, clefts between nasal opening and border of the beak, cleft palate of various degrees, strong reduction of the lower beak, reduction of size of the eyes, suppression of scleral papillae, reduction of eyelids, retardation in the development of embryonal pterylosis, suppression of feather anlagen.Apart from metric criteria, the development of nasal clefts is treatment-phase dependent. Such a phase specifity is recognizable in the outer appearance of strongly malformed hind legs too. The alterations due to TEM treatment between the 3 1/2the and 4 1/2th day of incubation on both sides of the sagittal plane are mirrorimages of a high degree.