Intact teratogenic immunoglobulins may reach the rat embryo

It is known that heterologous antiserum against rat kidney homogenate may induce congenital malformations when injected into pregnant rats during the period of organogenesis. Teratogenic rabbit antibodies against a purified rat renal tubular glycoprotein were isolated, labelled with 125I and injected into pregnant rats on the 10th day of gestation. Extracts of visceral yolk-sacs (VYS) and embryos were obtained 16 h later and chromatographed separately on a Sephacryl S-300 gel filtration column. The resultant chromatograms showed several radioactive peaks, one of which coincided with the eluate of intact rabbit immunoglobulins G (IgG). We interpret the result as an indication that some undigested intact teratogenic IgG were present in VYS and the embryo.     

The localization of tellurium in tellurium-induced hydrocephalus

Résumé L'étude présente concerne la localisation du tellure dans le cytoplasme de cellules nerveuses ftales et post-natales chez des animaux dont la mère a ingéré du tellure durant la grossesse.

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This work was supported by USPHS research grant No. NSO-8891.     

The target period during fetal life for the production of tellurium hydrocephalus

Résumé Le terme de «target period», qui peut se traduire par période-cible, signifie la période de grossesse la plus sensible aux effets nocifs d'un agent tératogène. Le présent travail situe chez le rat la période-cible du tellure entre les 10^e et 15^e jours de la grossesse.

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This work is supported by grant No. NS 8891-01 from the U.S. Public Health Service.     

Postimplantation embryo culture for the assessment of the teratogenic potential and potency of compounds

Whole rat embryos cultured during the early stages of organogenesis were subjected to a panel of selected chemicals. Of seventeen known in vivo teratogens, seventeen also induced specific malformations in embryos grown in culture. Of ten chemicals which were reported to be negative in in vivo rat teratogenicity studies, eight also did not provoke dysmorphogenic effects in vitro. Of five additionally tested retinoids, all induced multiple malformations. However, concentrations used to induce these effects varied considerably, isotretinoin inducing malformations at 10(-5) M and arotinoid at 10(-11) M. The results indicate qualitatively as well as quantitatively a high predictability of this in vitro system and suggest that the postimplantation embryo culture system may also be useful in the prospective testing of new drugs and environmental chemicals.     

Postimplantation embryo culture for the assessment of the teratogenic potential and potency of compounds

Summary Whole rat embryos cultured during the early stages of organogenesis were subjected to a panel of selected chemicals. Of seventeen known in vivo teratogens, seventeen also induced specific malformations in embryos grown in culture. Of ten chemicals which were reported to be negative in in vivo rat teratogenicity studies, eight also did not provoke dysmorphogenic effects in vitro. Of five additionally tested retinoids, all induced multiple malformations. However, concentrations used to induce these effects varied considerably, isotretinoin inducing malformations at 10^–5M and arotinoid at 10^–11M. The results indicate qualitatively as well as quantitatively a high predictability of this in vitro system and suggest that the postimplantation embryo culture system may also be useful in the prospective testing of new drugs and environmental chemicals.     

Deciduoma induction in the rat by X-irradiation

Riassunto Una dose di 500–1000 r di raggi X, data localmente ad un lato dell'addome di ratte al quinto giorno di pseudogravidanza, ha stimolato la formazione di deciduomi nel corno uterino irradiato di metà degli animali. L'esame istologico ha rivelato che i deciduomi presentavano tipiche caratteristiche isto-morfologiche, ma erano 1/2-1/4 delle dimensioni medie dei deciduomi indotti traumaticamente. La formazione di un deciduoma anche in un corno dalla parte non irradiata potrebbe indicare che, sia un fattore locale che uno generale contribuiscono al meccanismo induttore.     

Critical period for induction of congenital hydrocephalus and dysplasia of subcommissural organ by prenatal X-irradiation in rats

A single whole-body X-irradiation of pregnant Wistar rats at a dose of 1.05 Gy at 10.30, 12.30 and 14.30 h respectively, of gestational day 10 resulted in significantly high incidences of hydrocephalic offspring. No hydrocephalic offspring resulted from X-irradiation of pregnant rats with 1.05 Gy at 16.30 h, whereas a dose of 1.22 Gy at 16.30 h resulted in a low but statistically significant incidence of hydrocephalus. Neither 1.05 Gy nor 1.22 Gy X-irradiation of pregnant rats at 18.30 h resulted in any hydrocephalic offspring. Dysplasia of the subcommissural organ was noticed in all the hydrocephalic brains histologically examined.     

Critical period for induction of congenital hydrocephalus and dysplasia of subcommissural organ by prenatal X-irradiation in rats

Summary A single whole-body X-irradiation of pregnant Wistar rats at a dose of 1.05 Gy at 10.30, 12.30 and 14.30 h respectively, of gestational day 10 resulted in significantly high incidences of hydrocephalic offspring. No hydrocephalic offspring resulted from X-irradiation of pregnant rats with 1.05 Gy at 16.30 h whereas a dose of 1.22 Gy at 16.30 h resulted in a low but statistically significant incidence of hydrocephalus. Neither 1.05 Gy nor 1.22 Gy X-irradiation of pregnant rats at 18.30 h resulted in any hydrocephalic offspring. Dysplasia of the subcommissural organ was noticed in all the hydrocephalic brains histologically examined.     

Metallothionein induction by cadmium and zinc in rat secretory organs

Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2-4.9 micrograms/g wet weight tissue while in the pancreas it was shown to be 15.2 micrograms/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Metallothionein induction by cadmium and zinc in rat secretory organs

Summary Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2–4.9 g/g wet weight tissue while in the pancreas it was shown to be 15.2 g/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.