Embryotoxicity of transplacentally and intraamniotically administered 6-azauridine in mice.
Embryotoxic effects were compared of intramuscularly (im) and intraamniotically (ia) administered 6-azauridine (Riboazauracil Spofa) in random-bred mice H-Velaz. Effects of single doses (0.25 mg, 2.5 mg, 25.0 mg and 250.0 mg for im and 0.0025 mg, 0.025 mg and 2.5 mg for ia administration) on days 11, 12, 13 and 14 were evaluated as a sum of dead fetuses and fetuses with cleft lip and/or palate, fetuses with limb deformities and fetuses with deformities constituting the syndrome of caudal regression (hypoplasia of the caudal part of the trunk, absent tail, short tail, curled tail). Considering the sensitivity peaks of the morphogenetic processes which were observed, the dose-response relationships, the transformation of the teratogenic to a lethal effect and critical period extension with increasing doses, it was found that the effects of ia and im administered 6-azauridine did not differ. It was concluded that ia administered 6-azauridine had direct effect on embryonic morphogenetic processes and that this, too, was the essential mechanism of embryotoxicity of im administered 6-azauridine. The value of the intraamniotic technique for establishing the direct embryotoxic effect is discussed.
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000650:Amnion; D000818:Animals; D001380:Azauridine / Q000008:administration & dosage / Q000633:toxicity*; D002971:Cleft Lip / Q000139:chemically induced; D002972:Cleft Palate / Q000139:chemically induced; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D007267:Injections; D007273:Injections, Intramuscular; D017880:Limb Deformities, Congenital; D051379:Mice; D011247:Pregnancy; D013623:Tail / Q000002:abnormalities; D013997:Time Factors
D001380:Azauridine