摘要:

AbstractThe effect of the heavy metal toxicants HgCl2, CH3HgCl, and CdCl2on the acetylating activity of membranous carnitine acetyltransferase (CarAc) in membrane vesicles from the maternal surface of human placental syncytiotrophoblast has been investigated. CarAc was inhibited by inorganic and organic mercury and cadmium. Carnitine acetylation was inhibited by as little as 5 μM mercury, with complete inhibition at 50 μM inorganic and organic mercury. Inhibition by cadmium was incomplete (<60%) at 500 μM CdCl2. Kinetic studies using Hanes plots revealed a mixed type of inhibition of CarAc by the metals. Cysteine preincubation decreased the amount of inhibition of CarAc by the metals. These results indicate that the inhibition of CarAc by heavy metals occurs by binding of the sulfhydryl on the enzyme by the metals. This interaction may be a mechanism of the heavy metal‐induced fetotoxi

ISSN:0270-3211    

DOI:10.1002/tcm.1770060502

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

年代:1986

数据来源: WILEY

摘要:

AbstractA test system for identifying toxicity, including potential teratogenicity has been developed that is based on growth and viability of embryonic, fetal, and postnatal mice (J. Toxicol Environ Health 10:541–550, 1982). To test the utility of this assay, a series of 55 compounds was administered to timed‐pregnant ICR/SIM mice during organogenesis. The test compounds included known teratogens, known nonteratogens, and equivocal teratogens. They represented a wide variety of classes including pesticides, organic solvents, metals, steroids, nutrients, food additives, antimetabolites, alkylating agents, and pharmaceutical agents. A single dose level, at or near the level producing overt maternal toxicity in preliminary range‐finding studies, was administered by gavage on gestation days 8 through 12. Females were allowed to deliver; litter size and weight on the day of birth and 2 days postpartum were recorded, and stillborns were examined. Dams that had not given birth by gestation days 21 or 22 were killed and their uteri were examined. The results confirmed a strong correlation between reported teratogenic activity and embryo/fetal viability, and/or postnatal growth and viability. The results indicate that this test system is an effective, cost‐efficient means of prioritizing compounds for more detailed teratogenicity

ISSN:0270-3211    

DOI:10.1002/tcm.1770060503

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe teratogenic potential of the fungicide dinocap was evaluated in CD‐1 mice. Pregnant mice were dosed by intubation with dinocap in corn oil on gestation days 7‐16. Doses used were 0, 5, 10, 20, 40, 80, and 120 mg/kg/day, based on day 6 weight. Dams were killed on day 18, at which time fetuses were counted, weighed, and preserved for necropsy or skeletal examination. The highest dose killed 80% of the dams dosed, while 29% of the dams in the 80 mg/kg group died during dosing. There was no dose‐related maternal mortality at lower doses. Net maternal weight gain was affected only at 80 mg/kg/day. There were no live fetuses at 120 mg/kg/day. The number of live fetuses per litter was decreased and resorptions increased at 80 mg/kg. Dose‐related decreases in gravid uterus weight and fetal weight were significant at all doses of dinocap. Cleft palate was found in fetuses at 5(1/234; 0.4%), 20(46/195; 23.6%), 40(140/185; 75.5%), and 80(63/85; 74.1%) mg/kg/day. There was a dose‐related increase in supernumerary ribs and a low frequency of exencephaly and umbilical hernia at high doses. This study shows that dinocap is teratogenic in the CD‐1 mouse at doses well below those causing matern

ISSN:0270-3211    

DOI:10.1002/tcm.1770060504

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

年代:1986

数据来源: WILEY

摘要:

AbstractHuman embryonic palatal mesenchyme (HEPM) is an established cell line that is presently under investigation as an in vitro prescreening assay used to determine the teratogenic potential of chemicals. We describe here general growth characteristics, karyotype, and cell cycle analysis of these cells. HEPM cells had plating efficiencies of<95% and displayed notable contact growth inhibition following an exponential growth phase that lasted for approximately 6 days. These cells had the diploid karyotype of a female human embryo. The chromosomal complement showed no dramatic change between passage 5 and 14. Flow cytofluorometry analysis using bromodeoxyuridine (BrdU) pulse labeling and a direct immunofluorescence anti‐BrdU FITC probe revealed that the total cell cycle transit time was approximately 22 hr: the duration of G1was 12.2 hr, S was 6.1 hr, and G2‐M lasted for 3.7 hr. The results indicate that HEPM cells met the criteria regarding karyotype stability that were assumed by the National Toxicology Program of the

ISSN:0270-3211    

DOI:10.1002/tcm.1770060505

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe teratogenic potential of the anticonvulsant drug carbamazepine was determined following chronic oral administration in two inbred mouse strains (SWR/J and LM/Bc). The drug was administered in the animal's diet in concentrations equivalent to 0, 1,000, 1,500, or 2,000 mg/kg body weight, with treatment starting 2 wks prior to mating and continuing throughout gestation. Fetal examination failed to reveal a significant pattern of malformation in either strain at any treatment level. Levels of plasma carbamazepine and its metabolite, carbamazepine‐10, 11‐epoxide, were determined by high pressure liquid chromatography. There was no correlation with either of these compounds and the incidence of fetal abnormality. The inherent teratogenicity of carbamazepine is significantly lower than that of other anticonvulsant drugs that have been similarly tested in an animal mo

ISSN:0270-3211    

DOI:10.1002/tcm.1770060506

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe embryopathic effects of high doses of ethanolamine were evaluated in pregnant Long‐Evans rats during the “critical period” or organogenesis. Ethanolamine was given by gavage at levels of 0, 500, 300, or 50 mg/kg/day (24%, 14.4%, or 2.4% of the LD50value). Ethanolamine caused dose‐dependent increases in intrauterine deaths, malformations, and intrauterine growth retardation. Embryolethality caused by 500 mg/kg of ethanolamine was not random: male pups contiguous to two male siblings (designated mMm) were almost quantitatively replaced by resorptions that were contiguous to two live male pups (designated mRm) (mMm pups constituted 6.7% of control implants and decreased to only 0.9% of group II implants while mRm resorptions increased from 0.3% in controls to 5.6% in group II dams). Intrauterine growth retardation and increases in gross structural anomalies (considered indicative of depressed fetal growth) more severely affected male than female offspring at all dose levels. Pups of either sex who were contiguous to male siblings were more adversely affected than those offspring contiguous to one or more female siblings. As ethanolamine was given prior to the period of greatest fetal growth and fetal sex steroidogenesis, it is suggested that intrauterine levels of female sex steroids (estradiol) enhance fetal repair of cellular damage while testosterone inhibits fetal repair or exacerbates previous embryonic damage by some unknown mechanism. Such interaction furthers the concept that intrauterine position affects the endpoints of developmental toxicity, as expressed at part

ISSN:0270-3211    

DOI:10.1002/tcm.1770060507

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

年代:1986

数据来源: WILEY

摘要:

AbstractIncreased incidences of supernumerary ribs (SNR) are a relatively common finding in standard teratology bioassays, and previous studies have indicated a possible correlation between their occurrence and general maternal stress. The present study describes the effects of immobilization stress on the induction of supernumerary ribs. To isolate the sensitive period of SNR induction, Sprague‐Dawley rats and CD‐1 mice were treated with 300 and 1,500 mg/kg, respectively, of sodium salicylate on single days 7–11 of gestation. In the rat, day 10 was found to be the sensitive period of lumbar rib induction (32% SNR vs 10% on other days) while day 9 was critical in the mouse (71% SNR vs<29% on other days). In a second set of experiments, maternal stress was accomplished by restraining two groups of gravid females in the supine position for 12 hours on the predetermined sensitive day. One group was immobilized from 9 am to 9 pm, while the second group was restrained from 9 pm to 9 am. Concurrent controls were food and water deprived for similar periods. Additional untreated controls were also included. An increase in supernumerary ribs was noted in stressed mice but not in rats. The 9 am to 9 pm mouse group exhibited the highest increase in supernumerary ribs (41%) as well as significant incidences of fused ribs and exencephaly. A significant linear relationship between maternal weight loss during treatment and increases in supernumerary ribs was also noted. Results suggest that for some compounds, supernumerary ribs may be the indirect result of agent‐induced, generalized maternal stress in the CD

ISSN:0270-3211    

DOI:10.1002/tcm.1770060508

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

年代:1986

数据来源: WILEY

摘要:

AbstractSirenomelia, a fusion of the lower extremities, is believed to result from a median, bilateral symmetric defect of the caudal portion of the embryo at a very early stage in development. Anomalies of the gastrointestinal and urogenital systems are commonly associated with this malformation. Sirenomelia is not an embryolethal condition but typically is incompatible with postnatal life when combined with the associated malformations. In this study, intravenous treatment of hamsters with a combination of cadmium and lead on the morning of the eighth day of gestation resulted in 1.4, 22.2, and 35.6% of the viable fetuses displaying sirenomelia in litters recovered on days 15, 12, and 10 of gestation, respectively. With the exception of several fetuses with exencephaly, most structures cranial to the level of the umbilicus were normal. Caudal abdominal and pelvic structures were severely affected, with agenesis or dysgenesis of the kidneys, bladder, umbilical arteries, and external genitalia frequently noted. The administration of a combination of cadmium and lead has proven to be an effective and consistent means of inducing sirenomelia in the golden hamster.

ISSN:0270-3211    

DOI:10.1002/tcm.1770060509

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe susceptibility of the face region of the chick embryo to the teratogenic action of intraamniotically injected hydrocortisone contrasts with the resistance of the limbs to its action while at the same time their dysmorphogenesis may be induced by other agents. Since glucocorticoid receptors were shown to mediate face teratogenesis, their development was investigated in freshly dissected limb buds of 3‐, 3.5, and 4‐day‐old chick embryos in comparison with the face region. The specific binding of3H‐dexamethasone to molybdate‐stabilized glucocorticoid receptors was estimated by the dextran‐coated charcoal method and complemented by cytologic analysis of mitotic activity in control and hydrocortisone‐treated embryos. The glucocorticoid receptors were found in both organ anlagen already on day 3 when their concentration in femtomoles per microgram DNA was significantly higher in the face region. Accordingly, on day 3 intraamniotic hydrocortisone inhibited the mitotic activity in the face without affecting the developing limbs. On days 3.5 and 4 the concentration of glucocorticoid receptors was similar in both organ anlagen. Administration of hydrocortisone on day 4 induced mitotic depression in the face as well as in the limbs. However, the degree of inhibition apppeared to be dependent upon the actual mitotic rate. In the face region where the mitotic activity culminated at that time, the inhibition was much deeper and longer‐lasting than in the developing limbs characterized by continuous decrease of proliferation rate in controls. These findings are consistent with a view that glucocorticoid receptors are a prerequisite, but not the only factor in receptor‐media

ISSN:0270-3211    

DOI:10.1002/tcm.1770060510

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

年代:1986

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770060511

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

年代:1986

数据来源: WILEY