bluuebunny/crossref_metadata_2025_split huggingface dataset:
2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin‐ induced cleft palate in the mouse: Evidence for alterations in palatal shelf fusion
Authors: Pratt Robert M. , Dencker Lennart , Diewert Virginia M. 
Published: February 2006

Abstract2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) causes a high percentage of cleft palate in fetuses when administered during organogenesis in certain strains of mice including the C57BL/6J, but not in certain other strains (AKR/J). The purpose of the present study was to examine various biochemical and morphological aspects of TCDD‐induced changes in the developing palatal shelves. Our results indicate that when TCDD (100 μg/kg) was given on individual days between days 8 and 10 of gestation, a high percentage of cleft palate was observed. Receptors specific for TCDD were detected in the C57BL/6J but not AKR/J palatal shelves. The amount of TCDD receptors is highest in the palatal shelves on day 13 as compared to other embryonic tissues including the liver. Examination of cryostat sections taken from embryos during the time of palatal elevation and fusion demonstrated that TCDD does not interfere with growth, elevation, or initial contact of the palatal shelves, but does interfere with firm adhesion and/or degeneration of the medial epithelial cells. Our results suggest that TCDD exerts a direct effect on the embryonic palatal shelves which results in formation of cleft palate.
The effect of acute maternal toxicity on fetal development in the mouse
Authors: Kavlock Robert J. , Chernoff Neil , Rogers Ellen H. 
Published: February 2006

AbstractThe effects of acute alterations in maternal health status upon fetal development were assessed following exposure of pregnant CD‐1 mice on day 8 of gestation to one of ten chemicals at doses calculated to exert either a low or a moderate degree of maternal lethality. The dams were killed on day 18 of gestation, and the fetuses were examined by routine teratological techniques. The chemicals were cacodylic acid, caffeine, deltamethrin, dinoseb, ethylene bisisothiocyanate sulfide (EBIS), endrin, guthion, kepone, sodium salicylate, and toxaphene. Three (cacodylic acid, EBIS, and kepone) produced dose‐related increases in the incidence of dams with completely resorbed litters. Prenatal mortality in litters that contained live fetuses at term was elevated only for one chemical (cacodylic acid). Fetal weight was reduced in three instances (cacodylic acid, endrin, and guthion), while the incidence of terata was markedly elevated for two (cacodylic acid and kepone). For two other chemicals (endrin and sodium salicylate), a low incidence was found of defects that were similar to defects induced by those chemicals in other species. These effects appear to be chemospecific in nature and not the result of some indirect maternal action. Thus, maternal health status, as measured by the incidence of lethality in the treated groups and by the magnitude of maternal weight gain in surviving females, presents no simple explanation for many manifestations of fetal toxicity. However, for seven chemicals (excluding deltamethrin, EBIS, and kepone) an increased incidence of supernumerary ribs was observed. For three of these seven chemicals (caffeine, dinoseb, and toxaphene). supernumerary ribs was the only observed fetal effect. There was a significant linear inverse‐relationship between maternal weight gain during gestation and the incidence of extra ribs in the treated groups compared to their respective controls. Under the experimental conditions of this study, it appears that the incidence of supernumerary ribs increased in response to a nonspecific maternal toxicity.
Mutagenic activation of 2‐aminofluorene by fluorescent light
Authors: White G. L. , Heflich R. H. 
Published: February 2006

AbstractTo determine the effect of artificially produced light on the direct mutagenicity of 2‐aminofluorene, that arylamine was irradiated with either sun, cool‐white, black, blue, or yellow fluorescent light or held in the dark prior to assaying for mutagenicity using Salmonella typhimurium strain TA98. The effectiveness of these exposures in potentiating the mutagenicity of 2‐aminofluorene was sun > black > cool‐white 〉 blue 〉 yellow ≃ dark. By varying the radiant flux densities produced by the lamps and using optical filters, wavelengths of light up to approximately 450 nm were found to be effective in the mutagenic potentiation. Studies using radical scavengers and oxygen modifiers indicated that the light‐induced mutagenicity was dependent on oxygen and that singlet oxygen may be an effective activator of 2‐aminofluorene. The mutagenicity of fluorene was not increased by exposure to light, while only sunlight potentiated the mutagenicity of 2‐acetylaminofluorene. This result suggested the importance of the primary amine in the mutagenic activation of 2‐aminofluorene by light. Light‐activated 2‐aminofluorene was less mutagenic in strains TA98NR and TA98/1,8‐DNP6 than in TA98. This observation, combined with the dependence of the photoactivation on oxygen and amino‐substitution, indicated that the light‐enhanced mutagenicity was at least partially due to N‐oxidized photoproducts. These studies indicate that the effect of light on environmental contaminants must be considered in assessing their genotoxic potential.
The embryotoxicity of cyclophosphamide in rabbits during the histiotrophic phase of nutrition
Authors: Claussen Uwe , Krengel Hans Georg , Hettwer Horst , Servos Gisela , Voelcker Georg 
Published: February 2006

AbstractAfter iv injection of cyclophosphamide (CP; 80 mg/kg) and dechlor‐CP (60 mg/kg) on the 9th day of gestation (histiotrophic phase of nutrition) in rabbits, the concentrations of activated CP and activated dechlor‐CP were determined fluorometrically in the maternal blood and in the yolk sac fluid. Activated CP and dechlor‐CP could be measured in the maternal blood but not in the yolk sac fluid. This holds true for both the free as well as the protein bound form. During the histiotrophic phase of nutrition on the 9th day of gestation, the yolk sac wall seems to be a barrier for activated CP and dechlor‐CP. This phenomenon has to be traced back on the oxazaphosphorinring activated in position C4 and not on the alkylating activity. Therefore, a direct effect of activated CP can be excluded as the main reason for the embryotoxicity of CP. Consequently, the effects of iv‐injected CP on the entoderm of the visceral layer of the yolk sac placenta were investigated. Three, 6, 12, and 24 hours after CP injection, the maternal animals were laparotomized and the entoderm of the visceral layer of the yolk sac placenta in the mesometral parts of the blastoderms were prepared for electron microscopy. Like in the control group, 3 hours after CP injection no differences are found. Six hours after CP injection, a relatively flat cell‐type can be observed, which is probably based on the reduced absorptive capability of the entoderm. Twelve hours after CP injection the entoderm cells are nearly uniformly of the columnar type; this is interpreted as a restored absorptive activity. Twenty‐four hours after CP injection the columnar form of the entoderm cells and the reduced pinocytotic activity are interpreted as a state of secretion. During the histiotrophic phase of nutrition (9th day of gestation in rabbits), CP‐induced inhibition of the absorptive activity of the entoderm cells might lead to a quantitatively and/or qualitatively changed nutrition of the developing embryo. This changed nutrition may be the source of the embryotoxic effects of CP.
pH‐Induced changes in mitotic and developmental patterns in sea urchin embryogenesis. II. Exposure of sperm
Authors: Pagano Giovanni , Cipollaro Maria , Corsale Giuliana , Esposito Agostino , Ragucci Enrica , Giordano Giovan Giacomo 
Published: February 2006

AbstractpH decrease and increase were tested for their ability to affect the fertilizing capacity of sea urchin sperm, as well as to induce developmental defects and mitotic abnormalities in the embryos generated by pretreated sperm.Seawater (sw) at different pH values was obtained by mixing acidified (HCl) sw and alkalinized (KOH) sw. Thereafter sperm were exposed to different pHs for a defined time interval, or subjected to inactivation, while suspended in sw at defined pHs, as long as their fertilizing capacity was maintained.The study was carried out over the pH range 5–9; sperm showed optimal fertilizing capacity between pH 6 and 7. Below pH 6 and above pH 8 a drop in the fertilizing capacity was observed, whereas at normal sw pH (8.0–8.2) sperm showed intermediate values.pH decrease in sperm suspension induced a reproducible increase in developmental defects and mitotic abnormalities in the offspring of pretreated sperm. This effect displayed a dose‐response relationship, which was most evident for pH ranging from 7 to 8. The effects of decreased pH were detected as well in terms of quantitative changes in mitotic activity, which decreased in embryos generated by sperm exposed to low pH (5–6).The results are consistent with the induction of genetic damage following exposure of sperm to low pHs. This observation suggests a genotoxic action of hydronium ions per se. Another possible explanation for the observed genotoxicity of decreased pH might be based on the pH‐dependent activity of several genotoxins present in sw at trace levels.
The mutagenicity of sodium bisulfite on base‐substitution strains of Salmonella typhimurium
Authors: De Giovanni‐Donnelly Rosalie 
Published: February 2006

AbstractThe mutagenic effects of sodium bisulfite on Salmonella typhimurium LT2 strains carrying the hisG46 allele were investigated. Treating the cells with 1 M sodium bisulfite in 0.2 M acetate buffer (pH 5.2) for various time intervals at 37°C resulted in an increase in the yield of mutants above the spontaneous level. The fold enhancement of the mutant yield and the fold enhancement of the mutant frequency were greatest for the parent strain hisG46 with wild type DNA repair; the derived strains with reduced repair capacity responded to a lesser degree. While sodium bisulfite was mutagenic when tested in liquid suspension assays, strain hisG46 did not respond when the standard Ames plate incorporation assay was used. The greater mutagenic response in repair‐proficient strains suggests that normal repair capacities may favor the mutagenic activity of sodium bisulfite. Transduction studies demonstrated that mutations of his+ were closely linked to the hisD gene, and probably were in the structural hisG gene itself.
Extrapolation of the evidence on teratogenicity of chemicals between humans and experimental animals: Chemicals other than drugs
Authors: Hemminki K. , Vineis P. 
Published: February 2006

AbstractEpidemiologic literature regarding the possible association between malformations and 23 exposures or occupations other than pharmaceutical products, was analysed. The qualitative level of scientific evidence was classified into four categories: high (ethanol, methylmercury, PCBs, laboratory work), limited (anesthetic gases, carbon monoxide), low (hexachlorophene, LSD, nitrous oxide, smelter work, tobacco), and inadequate (all other exposures). Human data for exposures belonging to categories “high” and “limited” were quantitatively compared to results of animal teratogenicity tests of the relevant chemicals. Ethanol, methyl‐mercury, and PCBs have caused malformations in experimental animals, and the effective doses have ranged from 0.2 to 8.0 times the effective human doses. Ethanol and PCBs caused similar types of lesions in some animal species as have been observed in humans.
Inhibition of metabolic cooperation by the anticonvulsants, diphenylhydantoin and phenobarbital
Authors: Jone Cyrenius M. , Erickson Laurie M. , Trosko James E. , Netzloff Michael L. , Chang Chia‐Cheng 
Published: February 2006

AbstractHigh densities of 6‐thioguanine‐sensitive Chinese hamster V79 cells reduce the recovery of co‐cultured 6‐thioguanine‐resistant cells through a form of intercellular communication (metabolic cooperation). Diphenylhydantoin and phenobarbital, suspected human and animal teratogens and tumor promoters, were able to inhibit intercellular communication at noncytotoxic doses. A potentiation was observed when a mixture of the two chemicals was used.
Increased carcinogen metabolism and survival of retrovirus‐infected fischer rat embryo cells following repetitive carcinogen treatment
Authors: Raineri R. , Poiley J. A. , Hillesund T. , Ernst M. K. , Tennant R. W. 
Published: February 2006

AbstractThe carcinogens N‐2‐acetylaminofluorene (AAF) and diethylnitrosamine (DEN) often give negative results when tested in the Fischer rat embryo cell survival assay with the standard single 72‐hour regimen, whereas another carcinogen, benzo(a)pyrene [B(a)P], may yield varied results between different laboratories and may require relatively high concentrations (compared with other polycyclic aromatic hydrocarbons) for a positive result to occur. Enhanced survivals (compared with controls) were 56% or less with these carcinogens. In place of the standard single 72‐hour treatment with test chemical, the cells were exposed to three consecutive 24‐hour treatments. The amount of B(a)P metabolized during the last of the three 24‐hour treatment periods was 3.2 times greater than that during the first 24‐hour period, indicating that an induction effect occurred. Furthermore, the total amount of metabolites of B(a)P formed with repetitive treatments was 2.1 times greater than with a single 72‐hour treatment. The total amount of AAF metabolites formed with repeated treatments was 1.6 times greater than with the single treatment regimen, although no induction effect was observed between treatment periods. Survival enhancement with the repetitive regimen increased to 181% with B(a)P, 172% with AAF, and 188% with DEN. With benzo(e)pyrene, anthracene, and pyrene, enhanced survival was 14% or less following the single treatment regimen and did not increase following repetitive treatments. When the carcinogen cinnamyl anthranilate was tested using repetitive treatments, survival enhancement was more than 100% at three of six doses, versus less than 0% when the standard single treatment regimen was used.
Teratogenicity of arotinoid ethyl ester (RO 13‐6298) in mice
Authors: Zimmermann Bernd , Stürje Helga , Tsambaos Dionysios 
Published: February 2006

AbstractArotinoid ethyl ester (RO 13‐6298) is a new and very potent retinoid that exerts a profound influence on epithelial and mesenchymal differentiation in doses 500 times lower than those of compounds of the first and second retinoid generation. In the present study the teratogenicity of arotinoid ethyl ester was investigated in NMRI mice employing different treatment schedules. Recording of abnormalities was performed on day 18 (day 0 = day of conception) according to Wilson and with cleared skeletal preparations.Intraperitoneal application of the drug at a dosage of 10 μg/kg/day for three consecutive days (days 9–11 or 12–14) caused severe malformations, particularly in the skeletal system and the cavernous organs. Skeletal elements were reduced in number, shortened, or abnormally shaped. Ossification was diminished. Atresiae of anus and urethra were frequent. Single application of 200 μg/kg between days 8 and 14 also caused multiple and severe malformations. However, no stagespecific pattern of abnormalities was detectable. Some skeletal malformations indicated more or less vulnerable stages that were in concordance with special developmental steps. Others, however, seemed to be equally susceptible over a longer period, eg, rays 1 and 5 of the hand or foot and the development of the mandibular joints. The pattern of abnormalities caused by these very low doses of RO 13‐6298 is comparable to that obtained with other retinoids and is achieved within the same relative dose‐response range. Preconceptional treatment of the animals did not induce any malformations.
Murine oocyte destruction following intraovarian treatment with 3‐methylcholanthrene or 7,12‐dimethylbenz(a)anthracene: Protection by alpha‐naphthoflavone
Authors: Shiromizu Kenji , Mattison Donald R. 
Published: February 2006

AbstractBilateral or unilateral intraovarian injection with the polycyclic aromatic hydrocarbons 3‐methylcholanthrene (3‐MC), or 7,12‐dimethylbenz(a)anthracene (DMBA) destroys oocytes in C57BL/6N and DBA/2N mice. The threshold for small oocyte destruction following bilateral intraovarian treatment with 3‐MC was between 0.1 and 1 μg/ovary in both DBA/2N and C57BL/6N mice. After intraovarian treatment with DMBA, a more potent ovotoxin, the thresholds for small oocyte destruction were between 0.01 and 0.1 μg/ovary. Calculated ED50's for small oocyte destruction following bilateral intraovarian treatment with 3‐MC were C57BL/6N, 0.33 μg/ovary; DBA/2N, 1.02 μg/ovary—for DMBA the ED50's were C57BL/6N, 0.11 μg/ovary; DBA/2N, 0.03 μg/ovary. Unilateral intraovarian treatment also destroyed oocytes in the treated ovary. Treatment with intraperitoneal alpha‐naphthoflavone (ANF), a competitive inhibitor of polycyclic aromatic hydrocarbon metabolism by microsomal monooxygenases, inhibited oocyte destruction. Intraovarian treatment with ANF decreased oocyte destruction produced by intraovarian DMBA. These data suggest that both 3‐MC and DMBA are indirect acting ovotoxins requiring metabolic activation before oocyte destruction occurs. In addition, these data also suggest that the ovary contains the enzymes necessary to biotransform xenobiotics like 3‐MC and DMBA to ovotoxic metabolites. Metabolic activation of xenobiotics to reactive products within the ovary may represent a special threat to the integrity of oocyte DNA.
Detection of sister chromatid exchanges induced by volatile genotoxicants
Authors: Tucker James D. , Xu Jing , Stewart John , Baciu Peter C. , Ong Tong‐Man 
Published: February 2006

AbstractTo test the recently developed method of exposing cells to volatile compounds, phytohemagglutinin‐stimulated human peripheral lymphocyte cultures were exposed to gaseous methyl bromide, ethylene oxide, and proplyene oxide, as well as diesel exhaust. The cultures were placed in sterile dialysis tubing and inserted into enclosed flasks containing additional culture medium. The test compounds (in gaseous state) were diluted with air and bubbled through the flasks for various lengths of time. The cells were then washed and incubated for a total of 75 h. The harvest was performed according to established procedures, and second‐division cells were scored for induction of sister chromatid exchanges (SCEs). The SCE frequency was more than doubled in the cultures treated with ethylene oxide and propylene oxide; methyl bromide also induced SCEs. Cultures treated with diesel exhaust showed an increase in the SCE frequency in cells from two of four donors tested. These results further substantiate the use of this method for detecting the induction of SCEs by airborne genotoxins.
Transplacental genetic and cytogenetic effects of alkylating agents in the mouse. II. Induction of chromosomal aberrations
Authors: Braun Rolf , Hüttner Edith , Schöneich Jörg 
Published: February 2006

AbstractSix monofunctional alkylating agents, trenimon, cyclophosphamide, and isoniazid were proven for transplacental cytogenetic activity in mouse embryos at day 10 of gestational age under the same conditions as used in the mammalian spot test. With the exception of isoniazid, all compounds led to an increase in the aberration frequencies in embryonal cells. The results were statistically not significant in the case of EMS, while all other chemicals showed a dose‐dependent clastogenic activity. After treatment with monofunctional alkylants, chromatid breaks were dominating, while polyfunctional compounds also produced chromatid exchanges, especially in the case of trenimon. ENU and DMS showed a very early aberration maximum 6 hr after injection. For both compounds, very similar dose‐response curves were found for induction of chromatid breaks in the dose range 10‐75 mg/kg. There is no correlation between the Swain‐Scott factors of monofunctional alkylants and their ability to induce chromosomal damage when compared in terms of pharmacological doses.A quantitative comparison of data found in the cytogenetic test in embryonal cells with those obtained in the mammalian spot test led to the conclusion that chromosomal mutations are of minor relevancy for the expression of recessive alleles in heterozygous mouse embryos. With this respect, the mammalian spot test must be considered as an in vivo test for the detection of gene mutations in somatic cells of the mouse.
Endotoxin‐induced hyperthermia in pregnant golden hamsters
Authors: Hilbelink D. R. , Chen L. T. , Bryant M. 
Published: February 2006

AbstractThe degree of elevation and the duration of induced fever following endotoxin treatment of pregnant golden hamsters were examined. A radiothermistor was surgically implanted in the abdomen of each animal on day 6 of pregnancy. The animals were intravenously treated with a bolus injection of saline or endotoxin (1, 10, 20, or 200 μg/kg) on the morning of day 8 of gestation. Abdominal temperatures were monitored at 15‐minute intervals on days 8 and 9 and at 1‐hour intervals on days 10 through 14 of gestation. The mean temperature of the salinetreated control animals was 37.2°C with a range from 36.5 to 38.2°C. The total number of viable fetuses, and the mean fetal weight of the 1‐μg/kg group were not significantly different from those of the saline controls, although a statistically significant monophasic temperature elevation did occur between 3 and 9 hr post‐treatment. Three of seven females that received 10 μg/kg had viable litters and exhibited a monophasic fever. The remaining four animals exhibited a biphasic fever and total resorption of all implanted fetuses. The first phase began 2.5 hr post‐treatment and lasted for 3–6 hr. The second phase began 12–15 hr post‐treatment and lasted for 15 to 25 hr. All animals receiving 20 or 200 μg/kg demonstrated similar multiple temperature elevations. Treatment of animals with >20 μg/kg resulted in total resorption of all implanted fetuses and maternal weight loss. Nonpregnant females treated with 20 μg/kg of endotoxin exhibited a biphasic temperature elevation; thus the second phase of the fever response can not be attributed to embryo death and resorption.