摘要:

AbstractMale Long‐Evans rats were injected with 0, 1, 3, or 6 mg/kg of cadmium chloride on the first day of life. Animals free of morphological stigmata at weaning were selected for study. Tissue concentrations of cadium and operant behavior under various fixed‐ratio (FR) schedules of reinforcement were evaluated when these rats were adults. Dose‐related increases in cadmium were present in the brains, livers, and kidneys. Dose‐related differences in behavior were most evident during the transition from fixed ratio 25 (FR 25 or 25 responses/reinforcer) to FR 75. An inverted U describes the relationship between response output during the transition to FR 75 and cadmium chloride dose:response output increased at 3 mg/kg and decreased at 6 mg/kg. The rate decreases were not correlated with weight loss that appeared after some of the animals exposed to 6 mg/kg reached 60 days of age. Challenge doses of damphetamine revealed no interaction between neonatal exposure to cadmium and d‐amphetamine. The occurrence of alterations in operatnt behavior in animals that appeared normal on a number of preweaning evaluations suggests that operant behavior in transition was sensitive to subtle effects not observed with other commonly used tests. The data provide evidence for delayed effects in the adult that are due to neonatal exposure t

ISSN:0040-3709    

DOI:10.1002/tera.1420340302

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe combination of sirenomelia and anencephaly was observed in a stillborn dizygotic twin. A review of the literature revealed no other patients reported to have both conditions. Various explanations concerning the genesis of sirenomelia, and also the combination with anencephaly, are discussed.

ISSN:0040-3709    

DOI:10.1002/tera.1420340303

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

年代:1986

数据来源: WILEY

摘要:

AbstractHuman fetal alcohol syndrome characteristics have been seen in the mouse fetus by several investigators who dosed the dam with only one or two doses of alcohol. The purpose of this study was to determine if the fetal effects of acute doses of alcohol (ethanol) are altered by aspirin. CD‐1 mice were given two IP doses of a 25% v/v solution of 95% ethanol/saline (2.5 hours apart) and intubated with 250 mg/kg aspirin. The treatment regimen, begun at 8 days, 4 hours gestation, consisted of either aspirin pretreatment 1 hour before or posttreatment 1 hour after the ethanol. Control animals were treated similarly and included vehicle only, ethanol/vehicle, and aspirin/vehicle groups. One group was untreated. On gestational day 18, the dams were killed and the uterine horns were examined for live, dead, and resorbed fetuses. The live were weighed and examined for external malformations and either skeletal or visceral abnormalities. With the litter as the unit of analysis, no significant difference was found in the number of dead and resorbed among groups. There was a significant difference (P<.01) in average fetal weight in the aspirinpreteated group. When the total number of fetuses affected was considered, the aspirin pretreatment group showed significantly (P<.05) more external and visceral malformations. The skeletal examination revealed a significant (P<.05) difference in anomalies plus delayed ossification in both groups treated with the aspirin/ethanol combination. No significant differences were seen in any category in the groups receiving aspirin alone or ethanol alone. These results indicate and additive effect of aspirin and ethanol on the developing CD‐1 mouse fe

ISSN:0040-3709    

DOI:10.1002/tera.1420340304

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe calcium salt of valproic acid (Valontin) has been proposed for use in the treatment of absence, myoclonic, and tonic clonic seizures of the primarily generalized type. The present study was conducted to determine the teratogenic potential of calcium valproate in rabbits. Groups of 20 Dutch‐belted rabbits were given oral doses of 50, 150, or 350 mg/kg on days 6–18 of gestation. A referece group was given 350 mg/kg sodium valproate and control groups were untreated or given vehicle alone. Animals were observed daily and body weights were recorded on gestation days 0, 6, 13, 18, and 30. Litter and fetal parameters were evaluated following uterotomies on day 30. No drug‐related clinical signs or deaths occurred. Postimplantation loss and the incidence of malformed vertebrae and ribs, rudimentary or absent pollices, and extra vertebrae and ribs were increased at 350 mg/kg with both calcium and sodium salts of valproic acid. At the 150‐mg/kg dose level, calcium valproate markedly increased the incidence of supernumerary ribs. No teratogenic or embryotoxic effects were seen with calcium valproate at 50 mg/kg. These data indicate that the sodium and calcium salts of valproic acid exhibit teratogenic potential in

ISSN:0040-3709    

DOI:10.1002/tera.1420340305

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

年代:1986

数据来源: WILEY

摘要:

AbstractAmetantrone acetate is an antineoplastic drug chemically described as 1,4‐bis [[2‐[(2‐hydroxyethyl)‐amino]ethyl]amino]‐9,10‐anthracenedione diacetate salt. The drug has activity against leukemia and solid tumors in animal models. The purpose of this study was to investigate the teratogenic potential in pregnant rats and rabbits when administered during the critical period of organogenesis. Daily doses of 1.5, 3.0, and 6.0 mk/kg were administered IP to pregnant rats on days 6 through 15 of gestation, and 0.2, 0.4, and 0.8 mg/kg to rabbits on days 6 through 18. Dose‐related weight loss occurred in both species during treatment as well as in the entire gestation period. Maternal and fetal parameters were evaluated upon uterotomies in rats on gestation day 20 and rabbits on day 28. In both species, there was dose‐related blue discoloration of abdominal viscerae and of skin at injection sites. In rats, fetal malformations and developmental variations were comparable between treated and control fetuses. However, the incidence of fetal malformations was increased in rabbits given 0.4 and 0.8 mg/kg but not at 0.2 mg/kg. Based on these data, ametantrone was considered teratogenic at dose levels of 0.4 mg/kg and a

ISSN:0040-3709    

DOI:10.1002/tera.1420340306

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe teratogenicity of caffeine, as well as two of its three dimethylated metabolites (theobromine and theophylline), has been established in animal studies. The third metabolite, paraxanthine, has not been reported as being tested for teratogenicity even though it is actually the major demethylated metabolite of caffeine metabolism in man. Pregnant C57BL/6J mice were treated i.p. with 175 or 300 mg/kg/day paraxanthine (1,7‐dimethylxanthine) dissolved in deionized water at 4 p.m. on day 11 and 9 a.m. on day 12 of gestation. All dams were sacrificed on day 18, and fetuses were fixed for Wilson's razor blade sectioning or double‐staining skeletal examination. A dose‐related increase in total malformations, primarily cleft palate and limb malformations, was found. The pattern of malformations was similar to that reported for caffeine, theobromine, and theophylline, i.e., an asymmetric response with the left forelimb most often affected. A 21% resorption and a 46% malformation rate was observed at 300 mg/kg/day of paraxanthine, indicating that paraxanthine was slightly less toxic to the embryo than caffeine. Therefore, the parent compound, caffeine, as well as all three of its dimethylated metabolites—paraxanthine, theophylline, and theobromine—are te

ISSN:0040-3709    

DOI:10.1002/tera.1420340307

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

年代:1986

数据来源: WILEY

摘要:

AbstractMale mice heterozygous for the dominant polydactyly genePdn(Polydactyly Nagoya) were crossed with normal or heterozygous females of the same strain. Pregnant females were treated with 5 mg/kg of cytosine arabinoside (Ara‐C) on day 12 of gestation. The offspring were removed on day 18 of gestation and examined for external malformations, and the fore‐ and hindlimbs were examined by means of bone‐ and cartilage‐stained cleared specimens.In +/+ xPdn/+ matings,Pdn/+ fetuses, bearing preaxial polydactyly of the distal phalangeal type in the hindlimb and deformity of the 1st digit in the forelimb, were obtained in about 50% of the nontreated group. In treated fetuses, however, the incidence of polydactyly and deformity of the 1st digit decreased to 1.4 and 10.1%, respectively. NontreatedPdn/Pdnfetuses exhibited preaxial polydactyly of the duplicated or triplicated metacarpal/metatarsal type both in the fore‐ and hindlimbs. In the treatedPdn/Pdnfetuses, the number of preaxial extra digits decreased in both limbs. Some hindlimbs of the treatedPdn/Pdnfetuses exhibited five metatarsals, normally.In the vitally stained specimens at 6 and 24 hours after injection of Ara‐C, preaxial marginal necrotic zones (fMI) were observed in almost all of the treated embryos from +/+ ×Pdn/ + matings. However, approximately half of the embyros did not exhibit fMI in the nontreated control group at the same stage. Those embryos deficient in fMI were regarded asPdn/ +.These findings indicated that a subteratogenic dose of Ara‐C prevented the genetic expression of polydactyly in almost allPdn/+ and some cases ofPdn/Pdnmice. In addition, the fMI had an important role in the morphogenesis of preaxial polydactyly of distal phalangeal typ

ISSN:0040-3709    

DOI:10.1002/tera.1420340308

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe volatile anesthetic halothane, when present at fertilization, dose‐dependently increases the incidence of abnormally developing sea urchin embryos at the first cell division. Microscopic examinations of eggs stained with aceto‐orcein or the DNA fluorochrome bisbenzimide and direct observations on isolated sperm aster complexes show that halothane induces polyspermy (multiple sperm entry) when present at fertilization. Experimental evidence suggests that anesthetic‐induced polyspermy involves impairment of both the fast (electrically mediated) and slow (morphological) blocks to multiple sperm entry. These observations clearly show that relatively brief exposures to halothane at fertilization cause polyspermy and that this effect is almost certainly responsible for the ensuing abnormal development observed at the first cell div

ISSN:0040-3709    

DOI:10.1002/tera.1420340309

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

年代:1986

数据来源: WILEY

摘要:

AbstractCyclophosphamide must be metabolically activated to produce malformations in limbs developing in culture; 4‐hydroperoxycyclophosphamide is an analog of the active metabolite of cyclophosphamide, that breaks down spontaneously in solution to form 4‐hydroxycyclophosphamide. To study the mechanism by which metabolites of cyclophosphamide produce limb malformations in vitro we determined the effects of exposure of cultured limb buds to 4‐hydroperoxycyclophosphamide. Fore‐ and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to 4‐hydroperoxycyclophosphamide for the first 20 hours of the culture period. Addition of 10 μg/ml of 4‐hydroperoxycyclophosphamide to forelimb or to hindlimb buds in culture produced limb reduction malformations. A dramatic decrease in total limb bone area in fore‐ and hindlimbs was observed with 10 μg/ml of 4‐hydroperoxycyclophosphamide. In forelimbs, the long bone area decreased and the paw area remained constant so that the relative contribution of the long bone area to total limb bone area was decreased. In hindlimbs treated with 10 μg/ml of 4‐hydroperoxycyclophosphamide, no paw skeleton was observed. The DNA, RNA, and protein contents of the limbs were not affected by exposure to 1 μg/ml of 4‐hydroperoxycyclophosphamide, but were decreased by exposure to 10 μg/ml of this compound. Exposure to the higher concentration of 4‐hydroperoxycyclophosphamide also decreased alkaline phosphatase activity, a marker for osteogenesis, in both fore‐ and hindlimbs; in contrast, neither concentration of 4‐hydroperoxycyclophosphamide had an effect on creatine phosphokinase activity, a marker for myogenesis. Thus, the higher concentration of 4‐hydroperoxycyclophosphamide had differential effects on enzyme markers for osteogenesis and myogenesis and, in the forelimbs, on the long bones relative to the paw skeleton. The limb reduction malformations produced by exposure in vivo to cyclophosphamide may be a consequence of sele

ISSN:0040-3709    

DOI:10.1002/tera.1420340310

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

年代:1986

数据来源: WILEY

摘要:

AbstractA decline in LDH activity from four‐cell to late blastocyst was demonstrated in pre‐embryos from F1 (C57 female × A2G male) female mice. An exposure to 0.5 or 1 μg/ml cadmium did not affect the in vitro development of the four‐cell pre‐embryos and morulae or their LDH activities. At 5 or 10 μg/ml cadmium, the in vitro development of the treated pre‐embryos was affected. Although most of the treated four‐cell pre‐embryos had proceeded to compaction, they became degenerated 24 h after treatment. The LDH activity of these degenerated pre‐embryos was higher than that in the control blastocysts. We propose that cadmium may interfere with the general energy metabolism of the cells. This causes a reduced rate of LDH degradation, leading to a slower decline in LDH activity in cadmium‐treated pre‐embryos. Failure of some critical biochemical processes after cadmium treatment may ultimately lead to the subsequent degeneration of t

ISSN:0040-3709    

DOI:10.1002/tera.1420340311

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

年代:1986

数据来源: WILEY