concanavalin-a and Abnormalities--Drug-Induced

Concanavalin A (Con A), a plant lectin, was injected iv into pregnant rats as a single dose of 5, 10 or 20 mg/kg on gestational day (GD) 8, to investigate developmental toxicity in foetuses at term and to examine histologically embryos between GD 10 and 12. There were high incidences of various malformations in the 10 and 20 mg/kg groups: externally, craniofacial dysplasia and closure defects of the ventral body wall; internally, anophthalmia and cardiovascular malformations; and in the skeleton, anomalies of the anterior region of the vertebrae and ribs. Histological examination revealed that neural crest cells (NCC) in the control embryos appeared to be streaming from the neural crest towards the ventral region on GD 10, 11 and 12, and reached the region of the branchial arches on GD 12. By contrast, those in the Con A-treated embryos were aggregated near the dorsal region on GD 10 and 11, and had not reached the destination even on GD 12. These findings suggest that pathogenesis of developmental toxicity of Con A in rats is associated with disturbance of NCC migration and inhibition of their pluripotentiality at the destination.

Topics: Abnormalities, Drug-Induced; Analysis of Variance; Animals; Body Weight; Bone and Bones; Brain; Cell Movement; Concanavalin A; Craniofacial Abnormalities; Embryonic and Fetal Development; Female; Gestational Age; Heart Defects, Congenital; Male; Neural Crest; Pregnancy; Rats; Rats, Sprague-Dawley

A toxin associated with Toxoplasma gondii infection was obtained from the trophozoites and culture medium used to propagate the parasite in cell cultures. The toxin, named Toxofactor (TF), administered parenterally or nonparenterally in adult mice, produces transient symptoms of lethargy, ruffled fur, and body weight loss. Organ changes which accompanied the outward symptoms included hepatosplenomegaly and involuted thymus. TF activity was detected in extracts of the blood, peritoneal fluid, liver, and spleen of infected mice. Severe damage to embryonal and fetal development was induced when TF was administered during pregnancy. Resorption, abortion, and congenital abnormalities were produced, dependent upon the stage of development at the time of exposure. Adult mice which had reacted to and recovered from an initial intraperitoneal injection to TF were protected against a secondary challenge from TF. Fetal development was also protected from damage when TF was used to challenge adults previously exposed to TF. Mouse and rabbit anti-TF sera neutralized TF activity in the adult. In no instance did control mice show any deleterious effect when exposed to soluble cell lysate from the uninfected cell line (BHK-21) used to propagate the organism plus the used medium from these same uninfected cells. TF activity was not attributed to bacterial, myocoplasmal, or viral contamination. TF toxic activity is labile to elevated temperature and high or low pH, which also destroy its protective properties. TF activity was sensitive to trypsin and was obtained in the elution fraction (alpha-methyl-D-mannoside) from affinity chromatography (concanavalin A-Sepharose 4B). Ultrafiltration indicated the molecular weight to be between 50,000 and 100,000. TF, apparently a glycoprotein, was quantitated for activity by a weight loss assay. A unit of activity was defined as the minimum quantity of TF (highest dilution) which produced at least a 10% average body weight loss in adult Nya:NYLAR female mice between days 7 and 12 post-intraperitoneal injection.

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Cells, Cultured; Concanavalin A; Female; Hydrogen-Ion Concentration; Mice; Mice, Inbred Strains; Molecular Weight; Pregnancy; Reproduction; Temperature; Toxins, Biological; Toxoplasmosis, Animal

Concanavalin A (con A) is teratogenic to rabbit embryos during gestational days 12--15. Intracoelomic injections of 40 microliter con A solution (4 microgram/microliter) were performed on rabbit embryos during gestational days 10--15. Control embryos received either 40 microliter of saline, sham injection or no treatment. Con A caused increased fetal resorptions on days 10 and 11, but malformation levels did not differ from controls. On days 12--15, con A produced craniofacial, trunk and limb anomalies. The highest percentage of malformation occurred on day 14. The defects were classified into four groups: (1) malformations of limbs including paw and digital dysplasias as well as fusions of the limbs to the head or body wall; (2) "closure" defects such as umbilical hernia, encephalocoele, exencephaly or ectopia cordis; (3) "contracture" defects such as club paws, extended knees, or clenched digits, which exhibited normal osseous and cartilaginous skeletons; and (4) miscellaneous, non-specific anomalies including fused or dysplastic sternebrae or ribs. Histologic analysis of selected 12-day embryos 4 to 18 hours post-injection was performed to ascertain potential sites of teratogenic action. At 12 hours ectodermal necrosis was observed in the limb buds adjacent to the apical ectodermal ridge. By 18 hours, the ectoderm had eroded, exposing the basal lamina to the amniotic fluid. Focal areas of mesenchymal necrosis were observed in association with the ectodermal erosion. The potential roles of amniocentesis and limb bud repair in the genesis of the malformations are discussed.

Topics: Abnormalities, Drug-Induced; Animals; Concanavalin A; Contracture; Ectoderm; Female; Fetal Resorption; Forelimb; Gestational Age; Hindlimb; Neural Tube Defects; Pregnancy; Rabbits

Topics: Abnormalities, Drug-Induced; Animals; Chick Embryo; Concanavalin A; Epithelial Cells; Epithelium; Nervous System; Nervous System Malformations; Surface Properties