acid-phosphatase and Abnormalities--Drug-Induced

Craniofacial malformations were induced in 256 embryos from 32 pregnant rats by a single intraperitoneal injection of 10 mg/kg etretinate at 8.5 days gestation. The litters developed several malformations including microtia, low set and dorsally placed outer ears, defective middle ear ossicles, short cochleas, defectively differentiated Meckel's cartilages, micrognathia, rudimentary malar bones, lateral facial clefts, fistulas, and skin tags, all of which tissues are derivatives of the first and second branchial arches. The teratogenically induced syndrome shows similarities to the mandibulofacial dysostosis syndrome in man. The defects were accompanied by a change in the histochemical differentiation and location of various enzymes in the craniofacial tissues.

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Alkaline Phosphatase; Animals; Cartilage; Dihydrolipoamide Dehydrogenase; Embryonic and Fetal Development; Epithelium; Etretinate; Face; Facial Bones; Female; Fetus; Gestational Age; Histocytochemistry; L-Lactate Dehydrogenase; Male; Mesoderm; Rats; Rats, Inbred Strains; Succinate Dehydrogenase

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Capsaicin; Fatty Acids, Unsaturated; Female; Fetus; Maternal-Fetal Exchange; Morphine; Pregnancy; Rats; Rats, Inbred Strains; Receptors, Opioid; Spinal Cord; Time Factors

The mechanism and site of teratogenic action of trypan blue on mammalian embryos was reinvestigated. The experiments to be presented include (1) an analysis of the effect of trypan blue treatment on the morphology of the early mouse egg cylinder, (2) a demonstration of the effect of dye treatment on the enzyme acid phosphatase of yolk sac epithelium using histochemical procedures. Results obtained from these experiments indicate that trypan blue injected into mothers on day 7 of gestational age leads, within 12 to 24 hours after treatment, to dramatic abnormalities in 90-95% of egg cylinders examined. The frequency of gross malformations obtained by this treatment is considerably less when litters are examined at later stages of gestation. Acid phosphatase activity in yolk sac epithelium is depressed by the dye treatment, but there is no difference between enzymatically depressed yolk sacs of malformed embryos and yolk sacs surrounding normally appearing litter mates both obtained from trypan blue treated mothers. The hypothesis that trypan blue may exert its teratogenic effect by the direct exposure of egg cylinder stages to the dye, and that some of the egg cylinders affected may subsequently repair, is recommended for further testing.

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Epithelium; Female; Hematoma; Histocytochemistry; Injections, Intraperitoneal; Mice; Microcephaly; Morphogenesis; Spinal Dysraphism; Teratogens; Trypan Blue; Vitelline Membrane

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Cell Membrane; Drug Interactions; Drug Synergism; Edema; Embryo Implantation; Esters; Female; Fetal Death; Glucuronidase; Hindlimb; Inflammation; Lysosomes; Male; Methanol; Mice; Nicotinic Acids; Pregnancy; Rats; Salicylates; Stimulation, Chemical

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Anura; Biotransformation; Enzyme Activation; Forelimb; Growth; Inclusion Bodies; Lysosomes; Metamorphosis, Biological; Models, Biological; Morpholines; Phosphoric Monoester Hydrolases; Polymers; Time Factors

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Adenosine Triphosphatases; Aging; Alkaline Phosphatase; Amino Acids; Animals; Bone and Bones; Female; Forelimb; Glycogen; Glycosaminoglycans; Hindlimb; Nucleotidases; Pregnancy; Rats; RNA; Syndactyly

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Endoderm; Extraembryonic Membranes; Female; Glucosephosphate Dehydrogenase; Histocytochemistry; Injections, Intraperitoneal; Placenta; Succinate Dehydrogenase; Thiamine Pyrophosphate; Trypan Blue

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Alkaline Phosphatase; Animals; Cell Differentiation; Central Nervous System; Diet; Embryo, Mammalian; Female; Fetal Death; Flavins; Gestational Age; Histocytochemistry; L-Lactate Dehydrogenase; Limb Deformities, Congenital; Macrophages; Mesoderm; Mitosis; Necrosis; Phagocytosis; Pregnancy; Pregnancy Complications; Rats; Riboflavin; Riboflavin Deficiency; Staining and Labeling; Succinate Dehydrogenase

A mechanism of mammalian teratogenesis involving inhibition of embryotrophic nutrition is suggested and exemplified by the action of trypan blue on pregnant rats. There is evidence for the localization of trypan blue in heterolysosomes of the epithelium of the visceral yolk sac, and our experiments indicate that the dye is an inhibitor of a selection of hydrolytic enzymes present in lysosomal fractions from homogenates of rat visceral yolk sac. It seems likely that trypan blue inhibits the intracellular digestion of embryotroph by the visceral yolk-sac epithelium; the conceptus may therefore be deprived of essential nutrients at critical stages of development.

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Deoxyribonucleases; Enzymes; Epithelial Cells; Extraembryonic Membranes; Female; Glucuronidase; Histocytochemistry; Lysosomes; Microscopy, Electron; Pregnancy; Pregnancy, Animal; Rats; Ribonucleases; Trypan Blue

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Extraembryonic Membranes; Female; Injections; Maternal-Fetal Exchange; Mice; Monoamine Oxidase; Pregnancy; Pregnancy, Animal; Trypan Blue; Vitelline Membrane

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Cell Differentiation; Electrophoresis; Embryo, Mammalian; Esterases; Female; Folic Acid Antagonists; Folic Acid Deficiency; Histocytochemistry; L-Lactate Dehydrogenase; Maternal-Fetal Exchange; Oxidoreductases; Placenta; Pregnancy; Pregnancy, Animal; Rats

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Diseases; Chick Embryo; Chickens; Collagen; Embryology; Histocytochemistry; Hydroxyproline; Insulin; Poultry; Proteins; Research; Tibia; Toxicology