摘要:

AbstractIn order to get more insight into the effects of teratogens on developing embryos, we investigated the protein synthesis patterns of the target organs isolated from teratogen‐treated embryos. Rat embryos were either irradiated in utero with either252Cf fission neutrons or60Co gamma rays on day 8 of gestation or treated in utero with a bis(dichloroacetyl)diamine (a chemical teratogen) on days 9 and 10. Hearts were removed from the embryos on day 12 and were incubated in vitro at 37°C in the presence of [35S]methionine for up to 8 hr. The newly synthesized labeled proteins were then analyzed qualitatively by two‐dimensional polyacryl‐amide gel electrophoresis. Enhanced and prolonged induction of a family of heat‐shock (stress) proteins with a molecular weight of about 70,000 (SP70s) was observed as compared with those of controls. Among the teratogen‐treated hearts, those with gross malformations already detectable at this early stage showed especially higher inductions of SP70s than did the others. The abnormal expression of SP70s observed in the present study appears to be a reflection of persisting cellular (tissue) damage inflicted by the teratogens, and the extent of the induction may be indicative of the degree and/or type of the damage. Such persisting defects in surviving cells, manifested by abnormal induction of SP70s in the present study, might be related to malformation of embryo

ISSN:0270-3211    

DOI:10.1002/tcm.1770080602

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe teratogenic potential of nicotine and a primary metabolite, cotinine, was examined with FETAX (Frog Embryo Teratogenesis Assay:Xenopus). Early embryos ofXenopus laeviswere exposed for 96 hr to nicotine or cotinine in two separate static renewal tests of each compound without addition of the metabolic activation system (MAS). Two static renewal tests of nicotine with the MAS were also conducted. Addition of the MAS to nicotine reduced the LC50from an average of 136 to 20 mg/L. However, the EC50(malformation) was increased from 0.4 to 5.8 mg/L upon activation. The LC50and EC50values for cotinine averaged 4,340 and 720 mg/L, respectively. Based on mortality/malformation index values, growth end points, and the types and severity of the induced malformations, nicotine and cotinine scored as potential teratogens. Metabolism of nicotine to more polar metabolites increased the nicotine concentration required to induce terata. The results are indicative of the versatility of FETAX in developmental toxicity testing.

ISSN:0270-3211    

DOI:10.1002/tcm.1770080603

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

年代:1988

数据来源: WILEY

摘要:

AbstractThis study examines sister chromatid exchange (SCE) induction by ascorbate, a weak in vitro SCE inducer which acts through free radical intermediates, and low doses of 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea (CCNU), a potent SCE inducer which acts primarily through DNA interstrand cross‐links. A small dose‐dependent increase in SCE was observed in human peripheral lymphocytes exposed to ascorbate in the 0.5–10 mM dose range for 59 hours, with significant slowing of cell cycle kinetics at concentrations at and above 5 mM. CCNU concentration was selected to approximate the maximal increase in SCE induced by ascorbate. SCE frequencies in cells exposed sequentially to both agents were not significantly different from expectations under an additivity‐of‐effect model based on SCE response to each agent individually. Despite clear differences in the types of lesions induced, ascorbate and CCNU appear to act independently to induce SCE in a manner consistent with, though not exclusive to, Painter's r

ISSN:0270-3211    

DOI:10.1002/tcm.1770080604

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

年代:1988

数据来源: WILEY

摘要:

AbstractNeonatal female NMRI mice were treated with daily doses of 10−2or 5 μg diethylstilbestrol (DES) on one or more of days 1–5 after birth. Using immunohistochemical techniques and a monoclonal antibody to the estrogen receptor, we demonstrated an estrogen‐induced precocious appearance of receptor protein in the nuclei of the uterovaginal epithelium. High levels of peroxidase activity and a pronounced stromal infiltration with peroxidase positive cells occurred in the uterine cervix and upper vagina after estrogen treatment. This regional restriction in peroxidase activity was similar to the regional restriction for estrogen‐induced epithelial abnormalities (heterotopic columnar epithelium, adenosis). A combined treatment with DES and corticosterone depressed peroxidase activity but not to the control level. The distribution of abnormal epithelium was similar in DES‐and DES‐corticosterone‐treated females. The conclusion is that neonatal estrogen treatment induces an epithelial receptor for estrogen and a high level of cervical peroxidase activity, but the relationship between these parameters and the appearance of abnormal cervicovaginal epithelial changes could not be settled in the

ISSN:0270-3211    

DOI:10.1002/tcm.1770080605

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

年代:1988

数据来源: WILEY

摘要:

AbstractSodium azide (SA) was tested on sea urchin embryos and gametes (Paracentrotus lividus). Developing embryos were exposed to SA (10−6to 10−3M) up to pluteus larval stage, or for shorter intervals before or after hatching. Developmental defects in SA‐exposed embryos consisted mainly of gut abnormalities, without any detectable differences between pre‐ or post‐hatch‐exposed embryos. SA‐induced damage to gut was exerted during gastrulation, as evident by lectin binding of extracellular matrix. No mitotic damage was observed in SA‐exposed embryos, nor could pH‐related variations be detected in SA‐induced embryotoxicity at pH's ranging from 8 to 6. Concurrently, no effect ensued in the exposure of unfertilized eggs to SA (10−5to 10−2M) both in terms of fertilization success and of offspring quality. When sperm were suspended in filtered seawater at pH's ranging from 8 to 6, and SA levels ranging from 10−5to 10−2M, fertilization success of SA‐exposed sperm appeared to be modulated by pH, by displaying three distinct dose‐response trends at pH 8, 7, or 6. The consequences of sperm pretreatment on offspring quality failed to show any significant SA‐induced changes on larval malformations or mortality, while confirming the previously reported pH‐induced increase of developmental defects in the offspring of acid‐exposed sperm (Pagano et al.:Teratogenes

ISSN:0270-3211    

DOI:10.1002/tcm.1770080606

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

年代:1988

数据来源: WILEY

摘要:

AbstractBenomyl, a benzimidazole fungicide, was administered by gavage to pregnant Sprague‐Dawley rats in a daily dose of 62.5 mg/kg of maternal body weight beginning at gestational day (GD) 7. Fetuses examined histologically at GD16 or GD20 revealed a high incidence of craniocerebral anomalies—82.6% of those examined at GD16 and 100% of those examined at GD20. Hydrocephalus occurred in 65.2% of fetuses examined at GD16 and in 58.8% at GD20 but was more severe in the GD20 fetuses. A second common anomaly, termed periventricular “overgrowth” (PVO), consisted of subependymal cell masses that in some fetuses obliterated normal subcortical structures. PVO occurred in 34.8% of fetuses examined at GD16 and 76.5% at GD20. The size of the subependymal masses and the regions involved were considerably greater in the GD20 than the GD16 fetuses. Less common anomalies in the GD20 fetuses were periventricular necrosis (41.2%), a single fetus with exencephaly and another with porencephaly.In the majority of malformed fetuses, the severity of hydrocephalus did not parallel the severity of PVO around the lateral and third ventricles. PVO involved tissues surrounding the cerebral aqueduct in 17.4% of GD16 fetuses and 38.2% of GD20 fetuses. This “overgrowth” distorted the cerebral aqueduct in a large number of fetuses with ventriculomegaly, and at GD20 moderate and severe ventriculomegaly was in every instance associated with a narrow or completely occluded cerebral aqueduct. These relationships suggest that PVO in the midbrain may play a role in the production of aqueductal stenosis and hydrocephalus in this experim

ISSN:0270-3211    

DOI:10.1002/tcm.1770080607

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

年代:1988

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770080601

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

年代:1988

数据来源: WILEY