摘要:

AbstractAn in vitro culture of chicken embryo is described: the embryos at the stage of gastrulation are explanted from eggs into transparent silicone chambers where they continue to develop normally under controlled conditions for additional 3 d. This period corresponds to 2‐5 wk of postconceptional age in the human embryo. In both the chick and man, this period is very sensitive to physicochemical perturbations which can lead to surviving malformations.Six chemical agents were tested with this culture: methotrexate, cadmium chloride, caffeine, phenobarbital, aspirin, and saccharin. Survival scores, growth perturbations, and early signs of anomalies of the nervous, skeletomotor, and cardiovascular systems were analyzed with respect to the used concentrations. The dose‐response curves were obtained with good precision and allowed a discrimination between the teratogenetic and unspecific toxic effects and a comparison of the toxic potency of the six drugs. The evaluation of one drug took, roughly, 3 wk, one technician, and about 150 eggs.The advantages (simplicity, rapidity, reproducibility, specificity, economy, no suffering, and no use of mature animals) and disadvantages (nonmammalian species, absence of detoxicating organs) of the method are discussed. The method is proposed as a routine teratogenicity and embryotoxicity test which allows primary screening of many compounds and which can thus substantially reduce the ultimate experiments that use pregnant mammalian fema

ISSN:0270-3211    

DOI:10.1002/tcm.1770070502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractA late‐onset degenerative disease in the cerebellum was produced in the offspring of mice exposed to 1 mg/kg of the direct‐acting DNA alkylating agent methylnirosourea (MNU) on day 16 of gestation. This intrauterine exposure to MNU also provoked a progressive retinal degeneration that was described elsewhere. Mild ataxia in the MNU‐exposed animals was expressed by 20 weeks of age. Although animals appeared normal in the immediate post‐natal period, quantitative histological evaluation of cerebellar coronal sections indicated that MNU‐exposed animals had a significantly greater number of pyknotic Purkinje cells than age‐matched controls. The number of pyknotic Purkinje cells declined with age in the drug exposed animals; however, the percentage of pyknotic Purkinje cells to total number of Purkinje cells still was greater in MNU‐induced animals at 36 weeks than in controls, suggesting that a slow degenerative process was ongoing in the MNU‐exposed animals. Furthermore, the folia were grossly disrupted in 90% of the older MNU‐exposed animals (ages greater than 12 weeks), suggesting permanent cerebellar disruption macroscopically. Such intrauterine exposure to low doses of alkylating agents may be potentially useful in modeling degenerative

ISSN:0270-3211    

DOI:10.1002/tcm.1770070503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe in vivo interaction of the hepatocarcinogen 1,1,2,2‐tetrachloroethane (1,1,2,2‐TTCE) with DNA, RNA, and proteins of male Wistar rats and BALB/c mice was measured 22 hr after i.p. injection. Covalent binding index (CBI) to liver DNA was about 500 and was comparable to those of carcinogens classified as moderate initiators. It was higher than those of other chloroethanes, even than that of 1,2‐ dichloroethane (1,2‐DCE), a symmetrically substituted haloethane whose genotoxicity has been widely demonstrated.In in vitro cell‐free systems, 1,1,2,2‐tetrachloroethane was bioactivated by mixed‐function oxidase(s) and glutathione‐S‐transferase(s) (GSH‐T) from microsomal and cytosolic fractions of rat and mouse liver and, to a lesser extent, of mouse lung. The in vitro activation led to formation of reactive species capable of binding to exogenous DNA and to the subcellular constituents of enzymatic fractions.These data, along with previous literature reports, provide sufficient evidence of 1,1,2,

ISSN:0270-3211    

DOI:10.1002/tcm.1770070504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractOur objectives were to determine whether the embryotoxic and teratogenic potential of cytosine arabinoside (Ara‐C) differs depending on the time of day. Pregnant CD‐1 (ICR) mice were placed in an environment where the phases of lighting and darkness were reversed by progressive phase‐delay or phase‐advance methods—2 h every day from day of gestation (dg) 2 to dg 7 (or 6). After it was confirmed that these progressive phase‐shifting methods had no effect on embryonic growth and pregnancy outcome, 5 mg/kg body weight (bt) of Ara‐C was injected intraperitoneally into these animals at 1000 or 1600 on dg 11, and the incidence of gross fetal malformations was compared with that in control dams treated similarly but under a regular lighting regimen (0600–1800). In contrast to previous reports on other teratogens, no diurnal difference was observed in fetal susceptibility to the teratogenic potential of Ara‐C. The possible usefulness of the progressive phase‐shifting method in the field of chronoter

ISSN:0270-3211    

DOI:10.1002/tcm.1770070505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractRat embryos of the CD strain were treated in a whole embryo culture system with either 30 or 40 μ1 of ethylene glycol (EG) per milliliter of culture medium for the first 8 (0–8 hr) or second 8 (8–16 hr) hr of a 48‐hr culture period. The compound was not embryolethal under these conditions but did alter growth and development. EG at 40 μ1/m1 of culture medium at 8–16 hr decreased morphological score, somite number, crown‐rump and head lengths, as well as DNA and protein contents. The most frequent abnormality induced by the compound was absence of yolk sac circulation; absent hindlimb bud, hypoplastic telencephalon, and lack of development of the otic and optic systems were also seen in EG‐exposed embryos. Since it has been reported that rodent embryos cultured in vitro lack alcohol and aldehyde dehydrogenases that metabolize EG, present results suggest that the parent compound is capable of altering normal embryonic development when administered during a brief period or

ISSN:0270-3211    

DOI:10.1002/tcm.1770070506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractPregnant female rats were exposed to antimony trichloride (0.1 and 1 mg/dl in their drinking water ad libitum) from the first day of pregnancy until weaning (22nd day after delivery). Pups were exposed to antimony trichloride (0.1 and 1 mg/dl in their drinking water ad libitum) from 22nd until 60th day of age. Antimony exposure did not significantly affect maternal and pup systolic arterial blood pressure, length of gestation, and number of newborn per litter. Antimony exposure decreased maternal and pup body weight. No macroscopic teratogenic effects have been observed. Whether or not pups were exposed to antimony trichloride, pressor responses to carotid occlusion and 1‐noradrenaline and hypotensive responses to 1‐isoprenaline and acetylcholine were significantly higher on the 60th than on the 30th day of age. In pups, prenatal and postnatal antimony exposure did not affect pressor response to carotidal occlusion, while it decreased pressor response to 1‐noradrenaline and hypotensive response to 1‐isoprenaline on the 60th day after birth. At last, antimony exposure at higher concentration decreased pup hypotensive response to acetylcholine on the 6

ISSN:0270-3211    

DOI:10.1002/tcm.1770070507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770070501

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY