bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aggregation patterns of fetal rat brain cells following exposure to X‐irradiation
Authors: Shoji R. , Suzuki K. , Lee I. P. 
Published: February 2006

AbstractIn our search for a simplified in vitro test system to assess the teratogenic effects of physical factors, we studied the effects of total maternal body X‐irradiation on aggregation patterns of enzymatically isolated fetal rat brain cells and on ultrastructural aggregate changes. The fetal brain cells were derived from day 14 gestation fetuses of pregnant Sprague‐Dawley (CD strain) rats exposed to X‐irradiation (25˙200 R) one hour prior to sacrifice. Notable changes in the cell aggregates following X‐irradiation included a reduction in cell aggregate size and an increase in number. The frequency of cell aggregates was higher in the treated than in the control group, and the mean diameter of cell aggregates was inversely related to increasing X‐irradiation doses. Transmission electron microscopy revealed in isolated cells features of degenerative processes which were similar to those found in intact fetal brain lesions caused by maternal X‐irradiation. Furthermore, scanning electron microscopy revealed that inhibition of cell aggregation following X‐irradiation could probably be attributed to inhibition of membrane filopodia development and a consequent failure of cell aggregates to fuse into a greater cell aggregate mass. These results suggest that the membrane factors which influence cell aggregation may be a useful parameter to assess early effects of X‐irradiation‐induced brain deformity. Presently, the cell aggregation culture system is being further evaluated as a short term test system for environmental teratogens.
Teratogenicity of valproic acid: In vivo and in vitro investigations
Authors: Kao J. , Brown N. A. , Schmid B. , Goulding E. H. , Fabro S. 
Published: February 2006

AbstractThe in vivo teratogenic potential of valproic acid was evaluated in the CD‐1 mouse. Dose selection was based on the estimated lethality curve and several doses were evaluated. Treatment during early organogenesis (Days 8–10) produced a dose related increase in congenital abnormalities which was accompanied by a decrease in fetal weight, Rib and vertebral abnormalities together with exencephaly were the most common defects. Greater embryo mortality was apparent following teatment during late organogenesis (Days 11–13), but the surviving fetuses were less sensitive to the dysmorphogenic effects and cleft palate was now the most common defect, Early neurula stage mouse (Day 9) and rat (Day 10) embryos were cultured in the presence of valproic acid (0.6–1.8 mM) for 48 hr. There was significant reduction in growth which was accompanied by a variety of dysmorphogenic effects. Irregular segmentation of somites together with incomplete and irregular fusion of brain folds were most evident. These were observed at concentrations of valproic acid where no adverse effects on the yolk sac circulatory system were apparent. These in vitro effects appear to be comparable to the in vivo observations and suggest a direct teratogenic action of valproic acid on the developing rodent embryo.
The lack of estrogen control of rodent alphafetoprotein levels
Authors: Sheehan Daniel M. , Branham William S. 
Published: February 2006

AbstractAlphafetoprotein (AFP) binding of estrogens is thought to protect fetal and neonatal rats from the toxic effects of high maternal estrogen levels. Since the plasma concentrations of several other steroid binding proteins are ligand regulated, we tested the hypothesis that estrogens regulate plasma AFP levels. A batch Sephadex equilibrium binding assay and Scatchard analysis were used to quantitate AFP in plasma of both adult mice (C3H/HeN MTV−) chronically fed diethylstilbestrol (DES) or estradiol (E2) and neonatal rats (CD) injected daily with E2 for the first 15 days of life. Estrogen treatment of adults did not increase AFP above the nondetectable adult levels, nor did it alter the plasma disappearance curve of neonatal AFP. In both adults and neonates, other estrogen responses were noted, demonstrating that the failure of biologically active estrogens to alter AFP levels is not due to insufficient amounts of estrogen. We suggest that estrogens do not alter patterns of AFP synthesis and degradation in the rat, a finding which contrasts with the general observation that steroids regulate the levels of their binding proteins.
Mutation induction and killing of prokaryotic and eukaryotic cells by 8‐methoxypsoralen, 4,5′‐dimethylangelicin, 5‐methylangelicin, 4′hydroxymethyl‐4,5′‐dimethylangelicin
Authors: Pani B. , Babudri N. , Venturini S. , Tamaro M. , Bordin F. , Monti‐Bragadin C. 
Published: February 2006

AbstractCell killing and induction of mutations were studied in V79 Chinese hamster cells and in Escherichia coli WP2 and WP2 uvrA as a result of treatment with four furocoumarins and near ultraviolet light (NUV). The results obtained on V79 Chinese hamster cells showed that the three angelicin derivatives tested have mutagenic as well as cytotoxic activity, although at different levels; 8‐methoxy‐psoralen (8‐MOP), which is the most cytotoxic drug, induces the lowest number of 6‐thioguanine (6‐TG) resistant mutants as a function of surviving fraction. The three angular furocoumarins, 4,5′‐dimethylangelicin, 5‐methylangelicin, and 4′‐hydroxymethyl‐4,5′‐dimethylangelicin, were found not to be bactericidal and only slightly mutagenic in excision‐proficient Escherichia coli. They were much more active in inducing cell death and mutations in Escherichia coli uvrA. On the contrary 8‐methoxypsoralen displayed mutagenic and cytotoxic activity in E. coli WP2 uvr+ as well as in E. coli uvrA. This study confirms that (1) mono‐adducts are efficiently repaired in excision‐proficient bacterial strains and (2) the nature of substituents could affect biological properties, such as mutagenic and cytotoxic activity, of furocoumarins.
Plasma membrane alterations due to promoters and antipromoters
Authors: Braun Andrew G. , Buckner Christine A. , Nichinson Bradley B. 
Published: February 2006

AbstractThe attachment of tumor cells to plastic surfaces coated with concanavalin A is inhibited by agents that either increase or decrease the apparent microviscosity of the plasma membrane. Since some promoters have been reported to decrease the plasma membrane microviscosity of treated cells, we have tested whether these agents inhibit tumor cell attachment. All 13 promoters tested were found to inhibit attachment at nontoxic concentrations. The apparent microviscosity of treated plasma membrane was reduced in the 11 cases where a measurement was possible. Eight of nine nonpromoting agents did not inhibit attachment. The exception, Aroclor 1254, was inhibitory on prolonged incubation. Finally, 10 of 13 antipromoting agents were found to also inhibit attachment. The apparent membrane microviscosity was increased following treatment with these inhibitory antipromoters. Thus, a consistent feature of promoter and antipromoter treatment is an alteration of the functional and the apparent fluid properties of the plasma membrane. These characteristics may be useful in the design of an in vitro assay for promoting activities in environmental samples.
Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing
Authors: Stuckhardt J. L. , Poppe S. M. 
Published: February 2006

AbstractA method for examining the viscera of rat and rabbit fetuses is described. Techniques used in detecting visceral alterations in rats and rabbits for routine teratogenicity screens have varied over the years. The method used should be quick and simple but at the same time must be accurate, reliable, and comprehensive. The procedure used in this lab is a complete and systematic necropsy of the fresh fetus requiring minimum equipment and time. The examination can be done immediately following cesarean section and yields an intact skeleton which can subsequently be processed for skeletal examination. The fresh specimen and the natural coloration of in situ organs makes color photography of visceral alterations clear and concise. Any lesion can be appropriately fixed for histopathic examination. This technique begins with the examination of the organs in the abdominal cavity and proceeds to the thorax. Of special interest is the procedure used to inspect the internal anatomy of the fresh fetal heart. A description of the internal examination of both rat and rabbit heads and eyes is also included.
Mutagenic and cytogenetic analyses of organic extracts of simulated runoffs from model coal piles
Authors: Stahl Ralph G. , Arrighi Frances E. , Matney Thomas S. , Bernard Gary S. , Johnston Dennis A. 
Published: February 2006

AbstractThe use of coal as a fuel in utility and other industries in the United States is increasing. Typically, these utilities store their coal outdoors in large piles, and rainfall on the piles produces a runoff containing hazardous inorganic and organic materials. Four coals of varying sulfur contents, all used for fuel in the United States, were tested. Organic materials were extracted from simulated runoffs of model coal piles and were tested for mutagenicity with a Salmonella/microsomal assay and for clastogenicity and cytotoxicity in Chinese hamster ovary cells. The extracts of the high‐sulfur coals and the lignite were more mutagenic and clastogenic than extracts from the low‐sulfur coal.
Two‐phase teratology study with the synthetic prostaglandin ONO‐802 given intravaginally to rats
Authors: Petrere Judith A. , Humphrey Ronald R. , Sakowski Raymond , Fitzgerald James E. , de la Iglesia Felix A. 
Published: February 2006

AbstractThe synthetic prostaglandin ONO‐802 was administered intravaginally to Sprague Dawley rats at doses of 1.0, 0.5, and 0.125 mg/kg on days 6 through 15 of gestation. A vehicle control group was treated with pessaries that did not contain the drug while another group remained untreated. Body weight, food, water consumption, and clinical signs were monitored during the experiment. In Phase One, 20 pregnant animals from each group were sacrificed at term, major organs were weighed, and litter and fetal data were collected. In Phase Two ten dams per group were allowed to deliver their litters, and the offspring were evaluated for survival, growth, developmental signs, and physiological function. Selected F1 offspring were retained to assess learning and emotional behavior or reproductive capacity.Administration of either 0.5 or 1.0 mg/kg of ONO‐802 resulted in a slight reduction in food consumption and body weight gain. Water consumption was increased both during and after the dosing period for the mid and high dose dams. Significantly increased weights for the heart, lungs, liver, adrenals, and ovaries and decreased weights for the thymus gland were noted at term sacrifice of the 1.0 mg/kg dams, whereas the 0.5 mg/kg group had increased weights of the adrenals and ovaries only. Litter parameters were unaffected by treatment. Weights of the female fetuses of the 1.0 and 0.5 mg/kg groups were significantly reduced when compared to controls. There were no significant drug‐related abnormalities among the F1 offspring and no evidence that treatment of the F0 dams affected the development, behavior, or reproductive performance of the F1 offspring. Thus, ONO‐802 was not teratogenic when given to rats by the intravaginal route.
Mutagenic, cytotoxic, and teratogenic effects of 2‐acetylaminofluorene and reactive metabolites in vitro
Authors: Faustman‐Watts Elaine M. , Yang Hsueh Ying L. , Namkung Moses J. , Greenaway Jean C. , Fantel Alan G. , Juchau Mont R. 
Published: February 2006

AbstractThe embryotoxic, mutagenic, and cytotoxic properties of 2‐acetylaminofluorene (AAF) and two of its reactive metabolites, N‐acetoxy‐2‐acetylaminofluorene (AAAF) and 2‐nitrosofluorene (NF) were assessed in vitro. A combined embryo culture/biotransformation system was used to determine the ability of these compounds to produce embryonic malformations, growth retardation, and/or embryolethality. Salmonella typhimurium auxotrophs (his−) were utilized to measure the mutagenic and cytotoxic potentials of these compounds.The parent compound, AAF, did not produce embryonic malformations or mutagenicity in the absence of an added cytochrome P‐450‐dependent monooxygenase system. Both metabolites produced each of the measured toxic effects without supplementation of a bioactivation system. However, the three chemicals each elicited a different spectrum of malformations. Bioactivated AAF produced neural tube abnormalities, whereas embryos treated with AAAF primarily exhibited prosencephalic malformations, and NF produced abnormalities of axial rotation or flexure. NF was approximately ten times more potent than AAAF as a direct‐acting mutagen but only slightly more active in producing embryonic malformations in vitro. The results indicated that differential effects on the various measured parameters could be produced by these chemicals. The results indicated further that neither NF nor AAAF appeared to be individually responsible for the neural tube abnormalities generated by biotransformed AAF.
Mouse limb bud development in submerged culture: Quantitative assessment of the effects of in vivo exposure to retinoic acid
Authors: Kwasigroch T. E. , Skalko R. G. , Church J. K. 
Published: February 2006

AbstractRetinoic acid, suspended in cottonseed oil, was administered via gavage to pregnant mice (ICR strain) on day 11 (E 11) of gestation at doses of either 20, 40, or 80 mg/kg. Fetuses were examined for external malformations on day 17 (E 17). Retinoic acid treatment induced micromelia (with the elimination of several long bones at higher doses) and digital defects (ectrodactyly and syndactyly) in a dose‐dependent manner in fetuses examined on day 17. Hindlimbs were affected more than forelimbs. In another group of experiments, limbs exposed to retinoic acid treatment in utero on E 11 were cultured on E 12 and maintained for 3 days in submerged culture. Cultured limbs were examined qualitatively for digital and long bone defects, and image analysis of the area and form of bone anlagen of cultured limbs was used to quantitatively evaluate the teratogenic potential of retinoic acid. The qualitative evaluation indicated that the retinoic acid‐induced effects obtained in vivo and with pretreated, cultured limbs were essentially the same, except that the severity of regional effects changed as a result of culture. The incidence of ectrodactyly was higher with cultured limbs than with E 17 fetal limbs, but fewer cultured limbs were missing long bones. These results suggest that culturing limbs, after they have been pretreated in utero, modifies their response to a teratogen and demonstrates that the paw skeleton is extremely sensitive to teratogen treatment under these experimental conditions. Therefore, care must be exercised when attempting to compare in vivo and in vitro teratogenic data. This study also clearly demonstrates the power and usefulness of image analysis for quantitative evaluation of both the area and form of a cultured specimen such as the developing limb bud. Quantitative, image analysis of cultured limbs showed a dose‐dependent decrease in area of both fore‐ and hindlimbs. The effect was most severe in hindlimbs. In the forelimb, the paw was affected more than the long bones; as the dose increased, this disparity of effect also increased. With the hindlimb, a greater effect on the paw occurred only at 80 mg/kg. Computing the soft tissue/bone ratio illustrated that retinoic acid had a greater effect on chondrogenic tissue than on soft tissue.
Developmental toxicity during the preimplantation period: Embryotoxicity and clastogenic effects of chlorambucil in the rat
Authors: Giavini E. , Bonanomi L. , Ornaghi F. 
Published: February 2006

AbstractTo evaluate the toxicological effects of chemicals on preimplantation mammalian embryos, pregnant rats were treated with chlorambucil (0, 3, 6, and 12 mg/kg IP) on day 1, 2, or 3 of gestation (positive vaginal smear = day 0). Blastocysts were collected on day 4 and evaluated for gross morphology, cell number, and mitotic index. Some females treated on day 3 post coitum were sacrificed on day 20 and fetuses were evaluated for teratogenic effects. On day 4 of gestation a dose‐related reduction of cell number/embryo was recorded; this effect was most manifest with treatment on day 3 post coitum. The mitotic index was significantly higher in all treated groups. A dose‐related increase in “micronucleus‐like bodies” has been observed in treated embryos. A comparison with the micronucleus test in the bone marrow revealed a major sensitivity of the embryonic material. No malformations have been observed in fetuses at term, but their weights were significantly reduced and a dose‐related increase of postimplantation loss was recorded in treated females.
Development of a mouse embryo limb bud cell culture system for the estimation of chemical teratogenic potential
Authors: Guntakatta M. , Matthews E. J. , Rundell J. O. 
Published: February 2006

AbstractHigh‐density cultures of mouse embryo limb bud cells differentiate and synthesize an extracellular matrix containing sulfated proteoglycans. Since these in vitro events are related to those that occur during fetal development, we have investigated the use of cultured limb bud cells for the analysis of the activities of chemical teratogens. We have established the conditions for the use of the radiochemicals 35SO and 3H‐thymidine for the assessment of chemical effects on sulfated proteoglycan and DNA synthesis, respectively, in mouse limb bud cells. By performing double‐labeling experiments in the presence of test chemicals, the preferential inhibition of either proteoglycan synthesis or DNA synthesis could be demonstrated for 19 of 22 known mouse teratogens tested. The five nonteratogens tested did not cause significant differences in the inhibition of either macromolecular class. The overall predictive accuracy of the system was ∼89%, and the false‐negative rate was ∼14.8%. No false positives were observed. These data showed that this cell culture system differentiated between the activites of a limited set of selected mouse teratogens and nonteratogens, suggesting that cultured mouse embryo limb bud cells may constitute the basis for the development of a powerful tool for analyses of chemical teratogenic potential.
Short‐term bioassays of fractionated emission samples from wood combustion
Authors: Alfheim I. , Becher G. , Hongslo J. K. , Lazaridis G. , Löfroth G. , Ramdahl T. , Rivedal E. , Salomaa S. , Sanner T. , Sorsa M. 
Published: February 2006

AbstractExtracts of an emission sample from wood burning, consisting of particles and volatiles, have been fractionated on an HPLC silica gel column into five fractions of increasing polarity. Nonfractionated samples and the individual fractions have been tested in three different short‐term bioassays: the Ames Salmonella assay, the sister chromatid exchange (SCE) induction‐test in Chinese hamster ovary cells (CHO), and the cell transformation test on Syrian hamster embryo (SHE) cells.Most of the total activity was found in the volatile part of the sample with all three bioassays, whereas the particle extract had the highest activity per unit mass extracted. The second most polar fraction contained most of the mass and was also highly active in all assays. The most polar fraction was very potent in the Salmonella assay, but showed only a weak response in the eukaryotic bioassays. Storage of the samples for several months at 0°C revealed that the bacterial mutagens present in the most polar fraction were labile; the mutagenicity was almost totally lost after 1 year's storage.
The effects of phenylalanine on cultured rat embryos
Authors: Walsh D. A. , Christian Z. H. 
Published: February 2006

AbstractThe offspring of mothers with untreated classic phenylketonuria (PKU) have shown a high frequency of microcephaly, mental retardation, pre‐ and postnatal growth retardation, and birth defects. The aim of this study was to determine whether phenylalanine (phe) is the teratogenic agent in maternal PKU.To observe the direct effects of phe on organogenesis, embryos of 9.5‐day pregnant rats were cultured for 48 h in the presence of phe at concentrations of 0.1 to 6.0 mM. Within this range no morphological abnormalities occurred in exposed embryos, when compared to control embryos. However there was a reduction (P ≤ 0.05) in embryonic protein content and somite number at the highest concentration of phe (6.0 mM). This does not preclude the longer‐term effects of phe at later stages of gestation.To examine phe transport into the embryo in response to elevated serum phe levels, 3H‐phe uptake studies were undertaken. These showed that 3H‐phe from the culture serum is incorporated rapidly into the free amino acid pools and embryonic protein. At serum concentrations of 1.4 mM or higher, phe saturation occurs in the cellular pools of the embryo. Amino acid analysis of the exocoelomic fluid showed that when embryos were cultured for 48 h in serum containing 3.45 mM phe, the total amino acid concentration was maintained near the control levels (16 mM). Of this, 27% (4.26 mM) was contributed by phe, and all other amino acids, except methionine, were decreased with respect to control levels.
Induction of chromosome aberrations and specific locus mutation but not sister chromatid exchanges in Chinese hamster ovary cells by neocarzinostatin
Authors: Au W. W. , O'Neill J. P. , Wang W. , Luippold H. E. , Preston R. J. 
Published: February 2006

AbstractThe induction of chromosome aberrations, sister chromatid exchanges (SCE), cytotoxicity, and 6‐thioguanine‐resistant mutation by neocarzinostatin (NCS) in Chinese hamster ovary cells was analyzed. It was observed that within the same concentration range of 0.01–0.1 μ/ml NCS, the drug induced a significant increase in all analyzed end‐points except in SCE frequencies. There was no increase in SCE frequencies even when the cells were treated at the G1/S border in the first cell cycle and when aberrations were observed in the same cell showing a second cycle differential staining pattern. Our study indicates that the cellular damage induced by NCS leads to expression in chromosome aberrations, cytotoxicity, and mutagenicity but not in sister chromatid exchanges.
DNA damage and repair in mouse embryos following treatment transplacentally with methylnitrosourea and methylmethanesulfonate
Authors: Jirakulsomchok Saowalak , Yielding K. Lermone 
Published: February 2006

AbstractMouse embryos were labeled in vivo at 10 1/2–12 1/2 days of gestation with [3H]‐thymidine and subjected to DNA damage using x‐ray, methylmethanesulfonate, or methylnitrosourea. DNA damage and its repair were assessed in specific cell preparations from embryos isolated at intervals thereafter using the highly sensitive method of nucleoid sedimentation, which evaluates the supercoiled state of the DNA. Repair of x‐ray damage was demonstrated using trypsin‐dispersed cells from whole embryos and from homogenized embryonic liver to show the validity of the analytical approach. The effects of the highly teratogenic methylnitrosourea and the much less teratogenic methylmethanesulfonate were compared in the targeted limb buds using equitoxic doses of the two alkylating agents. DNA supercoiling was fully restored after 24 hr in limb bud cells damaged with methylmethanesulfonate, while as much as 48 hr were required for full repair of methylnitrosourea damage. These results demonstrated the feasibility of studying DNA repair in embryonic tissues after damage in vivo and suggest that the potency of methylnitrosourea as a teratogen may be correlated with a prolonged period required for complete repair of DNA.