bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assay of mutagens in aqueous fecal extracts with a modified ames Salmonella test
Authors: Shaw Roger , Andrews A. W. , Riggs Charles W. 
Published: February 2006

AbstractMutagenicity with Salmonella strain TA 100 can be determined by an island test in which only an isolated portion of a pour plate is spotted with a sample. The magnitude of the ratio of the numbers of revertant colonies on the treated and untreated parts of the plate reflects the potency of the mutagen. Five of six chemicals tested yielded statistically significant and generally linear dose‐response curves. Minimum detectable mutagenic doses for four compounds calculated from the dose‐response curves showed that the island test generally required less material for detection of mutagenicity than the liquid pre‐incubation procedure. The island method was primarily designed to test the mutagenicity of aqueous extracts of human stool samples. Dose‐responses were obtained for six such samples, and in two samples the amount of material needed for a positive response was significantly less than that required in the liquid pre‐incubation method.
Effects of vitamins A, C, and E on aflatoxin B1‐induced mutagenesis in Salmonella typhimurium TA‐98 and TA‐100
Authors: Raina Vijay , Gurtoo H. L. 
Published: February 2006

AbstractThe effects of retinoids (vitamin A analogs) and vitamins C and E on the aflatoxin B1 (AFB1)‐induced mutagenesis in Salmonella typhimurium TA‐98 and TA‐100 were investigated. The bioassay was performed under conditions that permitted the effects of vitamins on carcinogen metabolism to be assessed separately from effects on the expression of the mutated bacterial cell.Both retinoic acid and retinol inhibited (up to 50%) AFB1‐induced mutagenesis in S. typhimurium TA‐98, but only retinol inhibited (up to 75%) mutagenesis in TA‐100. Retinoic acid inhibition of mutagenesis in S. typhimurium TA‐98 was pronounced over a wide concentration range (i.e., 2 × 10−10 to 2 × 10−8 M) however, at the higher concentrations (i.e., 2 × 10−8 to 2 × 10−6 M range) the predominant effect was the inhibition of the metabolism of AFB1 to its mutagenic metabolites. Vitamin E was more potent in inhibiting the expression of AFB1‐induced mutagenesis than vitamin C. However, the major inhibitory effects of vitamin E were related to the metabolism of AFB1, whereas vitamin C was inhibitory at both metabolic and the post‐metabolic levels of the AFB1 mutagenesis assay.The results of these investigations suggest that vitamins A, C, or E inhibit both AFB1 metabolism to its mutagenic metabolites as well as the expression of AFB1‐induced mutated bacterial cells.
Vascular anomalies and pyrimethamine‐induced malformations in the rat
Authors: Tangapregassom Anne‐Marie , Tangapregassom Marie‐Joseph , Horvath Cécilia , Trecul Michèle , Boucher‐Ehrensperger Maud , Petter Claude 
Published: February 2006

AbstractPyrimethamine injected into the rat on days 12, 13, and 14 of gestation induces several types of malformations, including limb and facial deformities. These malformations appear in the same location as the hemorrhages and hematomas induced by this substance. In order to visualize the extent of the vascular disorders in the affected areas, a polymerizable substance was injected intravenously into the fetus. After pyrimethamine treatment, the fetal vascular network was simplified and reorganized in a different way according to the severity of the malformations. The appearance of vascular pathology, followed by malformations in the same regions, raises the hypothesis of a vascular cause of fetal defects.
Supraadditive formation of micronuclei in preimplantation mouse embryos in vitro after combined treatment with X‐rays and caffeine
Authors: Müller W.‐U. , Streffer C. , Wurm R. 
Published: February 2006

AbstractThe influence of caffeine (0.1 or 2 mM), X‐rays (0.24 Gy [ = 25 R] or 0.94 Gy [ = 100 R]), or of a combination of both on the formation of micronuclei in early stages of preimplantation mouse embryos in vitro was studied. X‐rays as well as caffeine induced micronuclei. The dose‐effect curve after irradiation was linear for the dose range measured (0–3.76 Gy; = 0–400 R). Caffeine did not induce micronuclei if the concentration was 1 mM or less; between 1 mM and 7 mM, however, there was a linear increase in the number of micronuclei. A considerable enhancement of the number of radiation‐induced micronuclei was observed when irradiation of the embryos was followed by a treatment with caffeine. Not only was the sum of the single effects exceeded by the combination effects, but the combination results even lay in the range of supraadditivity of the envelope of additivity.
Analysis of the activity of DNA, RNA, and protein synthesis inhibitors on Xenopus embryo development
Authors: Courchesne Cheryl L. , Bantle John A. 
Published: February 2006

AbstractThe teratogenic and growth‐inhibiting potential of DNA, RNA, and protein synthesis inhibitors was explored using the Frog Embryo Teratogenesis Assay: Xenopus (FETAX). Endpoints measured in 96‐h static tests were survival, malformation, ability to swim, skin pigmentation, stage of development, and growth. The DNA synthesis inhibitors hydroxyurea, cytosine arabinoside, and ethidium bromide proved to be teratogenic by the severity of malformations induced. Hydroxyurea gave an LC50 of 1.82 mg/ml, an EC50 (malformation) of 0.43 mg/ml, while the values for cytosine arabinsode were 5.41 and 0.76, respectively. The values for ethidium bromide were 0.05 and 0.035. The RNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide were more embryolethal than teratogenic but significantly inhibited growth as determined by head‐tail length measurements. Actinomycin D caused severe malformations, while cycloheximide caused relatively minor abnormalities. The LC50 for actinomycin D was 1.89 mg/ml, while the EC50 (malformation) was 2.17 mg/ml. For cycloheximide, the values were 1.59 and 1.19, respectively. FETAX advantages include rapid data collection, the ability to measure stage‐dependent effects, and the ability to use a large number of embryos to obtain excellent doseresponse curves with narrow confidence limits. Disadvantages include lack of a metabolic activation system, absence of a placental relationship, and the inability to detect specific abnormalities such as limb defects in 96 h.
Propyldazine is mutagenic in Salmonella typhimurium and Escherichia coli: Distinct specificity for strains TA1537 AND TA97
Authors: Glatt Hansruedi , Oesch Franz 
Published: February 2006

AbstractThe antihypertensive drug propyldazine (Atensil) was demonstrated to be muta‐ genic with auxotrophic mutants of Salmonella typhimurium and Escherichia coli. Addition of liver S9 mix (postmitochondrial supernatant fraction supplemented with an NADPH‐generating system) had little, if any, effect on the mutagenicity. The mutagenicity showed an unusual pattern of strain specificity. Increased fre‐ quencies of reversion were observed with all strains whose auxotrophy was caused by frame‐shift mutations: the number of revertant colonies per plate from S. typhimurium TA98, TA1538, TA97, and TA1537 was increased up to 5‐, 9‐, 43‐, and 160‐fold, respectively, above background. Among the strains that became auxotrophic by substitution mutations, S typhimurium TA102, E. coli WP2, and E coli WP2 uvrA yielded positive results (twofold above background). S. typhimurium TA1535 and TA100 were not reverted by propyldazine.It should be noted that propyldazine, due to its low toxicity and good solubility, could be tested up to very high doses. Hence, although quite impressive mutagenic effects occurred, the mutagenic potency was moderate even in the most responsive strains, TA1537 and TA97 (about 0.3 and 1.0 revertants per nmole, respectively). With the limitation that the strain specificities were different, the mutagenic potency of propyldazine was in the same order of magnitude as that of hydralazine and dihydralazine, two related antihypertensive drugs which were already known to be mutagenic. In our hands, both compounds were mutagenic in S typhimurium TA1535, TA100, TA1537, and TA98. These results differ from data in the literature in that we found clear but weak effects even with strains for which others have reported negative results.
A critical comparison of the freehand razor‐blade dissection method according to Wilson with an in situ sectioning method for rat fetuses
Authors: Sterz H. , Lehmann H. 
Published: February 2006

AbstractTwo methods of dissecting rat fetuses are compared: the generally well‐known freehand razor‐blade dissection method according to Wilson and an in situ sectioning method (ISM). For this purpose the substance EGYT 1978 was used, which induces—inter alia—cardiovascular anomalies. Thirty‐nine gravid rats were given either the test drug (EGYT 1978, 400 mg/kg body weight) or the vehicle orally from the 6th to the 15th day of gestation. The fetuses were assigned randomly to either dissection group. Both methods of examination revealed approximately the same number of anomalies per organ system. A comparison of the types of anomaly found showed, however, relevant differences in the nature of the changes revealed by the two methods. The in situ sectioning method was clearly superior to the freehand razor‐blade dissection method for the detection of discrete anomalies of the cardiovascular system. We therefore recommend the in situ sectioning method as the method of choice for examining small fetuses from teratological experiments.
Teratogenic profile of retinylidene methyl nitrone and retinol in Swiss‐Webster mice
Authors: Willhite Calvin C. , Balogh‐Nair Valeria 
Published: February 2006

AbstractA single oral dose of 75 mg/kg of all‐trans‐retinol or all‐trans‐retinylidene methyl nitrone, retinoids with potential cancer chemopreventive properties, on one of five successive days of embryogenesis resulted in a shift in the pattern of developmental anomalies in fetal mice. Treatment on days 7, 8, or 9 with retinol primarily induced malformations of the head whereas treatment on day 11 induced bilateral forelimb reduction defects. Treatment on day 8 with either retinoid produced the highest in utero death rate. Intubation of either retinoid on day 10 failed to induce a significant increase in the number of litters containing offspring with malformations, and the embryonic death rate declined to control values. The malformations induced by administration of either retinoid were similar, but retinol was always associated with a higher total percentage of malformed offspring. The similar teratogenic profile of these two retinoids may be related to their in vivo biotransformation to all‐trans‐retinoic acid.
An analysis of lung cancer risk from exposure to hexavalent chromium
Authors: Braver Elisa R. , Infante Peter , Chu Kenneth 
Published: February 2006

AbstractLung cancer risk in relation to airborne levels of hexavalent chromium was analyzed for chromium chemical production workers studied by Hayes, Lilienfeld, and Snell. Hayes et al [18] had observed statistically significant increases in lung cancer mortality among chromium chemical production workers hired during 1945–1959 and followed to mid‐1977. A dose‐response was observed by Hayes et al. in that long‐term workers had a higher lung cancer risk than short‐term workers. Concurrent exposure data for the study plant were abstracted from the records of a local health department. The usual air concentration of hexavalent chromium was estimated as 413 micrograms per cubic meter (μg/m3) during 1945–1949. Cumulative exposure estimates for individual workers could not be developed with available information. Instead, cumulative exposures in terms of μg/m3‐years were estimated for groups of short‐term workers and long‐term workers (cumulative exposure = usual exposure level in μg/m3 × average length of exposure). For workers hired during 1945–1949, cumulative exposures were estimated as 670 and 3,647 μg/m3‐years for short‐term and long‐term workers, respectively. Like most estimates based on historical data, these exposure estimates are subject to uncertainty. Nevertheless, these results suggest a potential excess risk of death from lung cancer among U.S. workers exposed to the current permissible exposure limit (PEL) for hexavalent chromium of 52 μg/m3 because such workers could accumulate exposures (μg/m3‐years) similar to those associated with excess risk in Hayes et al's cohort. Moreover, many current workers are estimated to be exposed to levels above the PEL. Further exploration of the dose‐response relationship for chromium carcinogenesis is indicated.
Carcinogenicity bioassays of bromoacetaldehyde and bromoethanol—potential metabolites of dibromoethane
Authors: Van Duuren Benjamin L. , Melchionne Susan , Kline Stanley A. , Seidman Irving 
Published: February 2006

Abstract1,2‐Dibromoethane (DBE) and two of its potential metabolites, bromoethanol (BE) and bromoacetaldehyde (BA), were tested for carcinogenicity in male and female B6C3F1 mice using 30 animals of each sex per group. The carcinogen DBE was included in this assay as a positive control. The compounds were administered in distilled drinking water using equimolar concentrations, 4 mmol, of the chemicals. The dose chosen was based on subchronic bioassays of three months' duration. The chronic tests were continued for ∼450 days in the case of DBE and ∼560 days for both BE and BA. DBE induced squamous carcinomas of the forestomach in 22 females and 26 males and squamous papillomas of the esophagus in 3 females. BE induced squamous papillomas of the forestomach only in 10 females and 9 males. BA did not induce a significant incidence of tumors of the forestomach. Significant tumor incidences at other sites were not observed in any groups including the distilled water control group. Based on these findings, it is unlikely that BE or BA are activated carcinogenic intermediates of DBE.
Potentiation of chemically induced cleft palate by ethanol ingestion during gestation in the mouse
Authors: Lee Melvin 
Published: February 2006

AbstractThe influence of ethanol consumption on cleft palate induction by methylmercury, cortisone, and retinyl acetate was investigated in Swiss white mice. Consumption of 20% ethanol throughout gestation significantly increased the incidence of cleft palate compared to water‐fed mice, when methylmercury was given on four consecutive days (days 9–12, 5 mg/kg of body weight). Ethanol also increased the incidence of cleft palate in mice given retinyl acetate (3,400 or 5,100 IU) on day 12, compared to retinol acetate‐treated mice given water, but did not affect cleft palate induction by cortisone (2.5 mg/d, days 8–11). Ethanol significantly reduced fetal weight in the presence or absence of the three teratogens, but the results do not support a hypothesis that growth retardation is directly responsible for the potentiating action of ethanol. It may be that ethanol acts to increase cleft palate induction by some teratogens by retarding fetal developmental processes.
Progressive proliferative changes in the oviduct of mice following developmental exposure to diethylstilbestrol
Authors: Newbold Retha R. , McLachlan John A. , Bullock Bill C. 
Published: February 2006

AbstractStructural malformation of the oviduct has been reported in experimental animal models and women following prenatal exposure to diethylstilbestrol (DES). To study histological changes in the oviduct in the absence of gross structural malformation, neonatal CD‐1 mice were treated with DES (2 μg/pup/day) on days 1–5 of age. Focal epithelial hyperplasia was present at 1 month of age in 16 out of 18 (89%) of the DES‐treated mice. At 4 months of age, general epithelial hyperplasia with multiple gland‐like structures into and through the muscle wall of the oviduct was observed in 90% of the treated mice; by 12 months of age, epithelial hyperplasia and pseudogland formation were seen in 100% of the DES‐exposed animals. Epithelial hyperplasia and gland formation were not observed in control mice. The alteration induced by DES in the differentiation and proliferation of mouse oviductal epithelium suggests that the oviduct is a target for DES toxic effects. In addition, there was a progression of the epithelial changes with age. The histological changes described in this study may be partially responsible for the decreased fertility previously reported in this mouse model. Similar changes in the oviduct of DES‐exposed women remain to be determined.
An assessment of the effects of cyclophosphamide and sodium valproate on the viability of preimplantation mouse embryos using the fluorescein diacetate test
Authors: Kola Ismail , Folb Peter I. 
Published: February 2006

AbstractThe fluorescein diacetate test is a measure of both esterase enzyme activity and membrane integrity and it has been shown to be useful in assessing the viability of a variety of cells cultured in vitro, mouse embryos after freezing and thawing, and mouse embryos grown under inadequate culture conditions. In this study, the effects were examined of cyclophosphamide and sodium valproate administered respectively to pregnant inbred CBA mice 60 h after fertilization, on the viability of 84‐h blastocysts. Cyclophosphamide 20 and 40 mg/kg bodyweight and sodium valproate 90 mg/kg significantly increased the number of nonviable blastocysts. Cyclophosphamide 4 mg/kg and sodium valproate 23 and 45 mg/kg did not adversely affect blastocyst viability. The intensity of embryo fluorescence correlated well with the subsequent development of the embryos in culture (r = 0.863; p < 0.001). The test had a sensitivity of 83% and a specificity of 100%. Exposure of embryos to fluorescein diacetate under the conditions of this experiment did not adversely influence the subsequent postimplantation development of 84‐h blastocysts cultured in vitro for a further 120 h. These findings suggest that the fluorescein diacetate test is a simple, rapid, and nontoxic procedure that may be useful in assessing the viability of preimplantation embryos after exposure to embryotoxic drugs and chemicals.
Effects on the fetal rat intestine of maternal malnutrition and exposure to nitrofen (2,4‐dichlorophenyl‐p‐nitrophenyl ether)
Authors: Mahboob Soltanali , Hoogenboom Elizabeth R. , Kavlock Robert J. , Zeman Frances J. 
Published: February 2006

AbstractThe effects of maternal protein‐energy malnutrition and exposure to nitrofen on selected aspects of intestinal morphology and function were studied in the fetal rat. Pregnant rats were fed, throughout gestation, diets containing 24% or 6% casein as the sole source of protein. Reduced total food intake produced protein‐energy malnutrition (PEM). Each diet group was divided in half and gavaged with either 12.5 mg nitrofen in corn oil/kg/day or corn oil carrier only from days 7 to 21 of gestation. Body weight, intestinal weight, length, and diameter were measured as were villus length (VL), villus width (VW), and number of villi per length of intestine (VMM). Protein (horseradish peroxidase) and lipid absorption were studied histochemically. Lactase and dipeptidase activities were determined in proximal, medial, and distal thirds of the intestine. Results showed that the restricted maternal diet resulted in reduced fetal body weight (BW), intestinal weight (IW) and length (IL), reduced IW/BW and IW/IL ratios, VH, and VMM. The VW was reduced only in the distal third. Protein and lipid absorption were unaffected. Lactase and dipeptidase activities were reduced. Maternal nitrofen exposure resulted in reduced body weight, intestinal size, and lipid absorption, with some evidence of interaction with the diet effects on enzyme activities. It is concluded that effects of maternal malnutrition were extensive, but that nitrofen exposure, at this dosage level, is not likely to contribute to the postnatal fetal mortality rate in either adequately nourished or malnourished rats.
An improved procedure for the efficient injection of radioactive steroids into mouse embryos
Authors: Hochner‐Celnikier Drorith , Monder Carl 
Published: February 2006

AbstractRetention of 3H‐moxestrol in mouse fetuses after transmaternal, intrafetal, and intraplacental injection were compared. Direct injection into the allantoic placenta resulted in greater retention of radioactivity by the fetus than the other modes of administration between 12 and 16 days of gestation. By this same criterion, intrafetal injection was best for older fetuses. Maternal injection was the least efficient way to transfer 3H‐moxestrol to the fetus.
Induction of sister chromatid exchanges and chromosome damage by gossypol in bone marrow cells of mice
Authors: Nayak B. N. , Buttar H. S. 
Published: February 2006

AbstractThe chromosome‐damaging potential of gossypol was evaluated by scoring sister chromatid exchanges (SCEs), determining the percentage of pulverized metaphases and the mitotic index in bone marrow cells of mice. Bone marrow cells were collected approximately 21 hours after the intraperitoneal (0,20,40,80, or 160 μg/g) and oral (0,40,80, or 160 μg/g) administration of gossypol acetic acid. Irrespective of the dosing schedule (single or multiple doses), the vehicle used (physiological saline, corn oil, or 10% aqueous ethanol), and the route of administration, the mean SCE count per cell was significantly higher (P < 0.05) in gossypol‐treated groups than their control counterparts. At 80 and 160 μg/g dose levels, the occurrence of metaphase chromosome pulverization was significantly greater, while mitotic index values were markedly lower than those of the corresponding control values. The results suggest that gossypol is a potentially mutagenic and clastogenic agent in murine bone marrow cells.
Maternal administration of cyclophosphamide induces chromosomal aberrations and inhibits cell number, histone synthesis, and DNA synthesis in preimplantation mouse embryos
Authors: Kola Ismail , Folb Peter I. , Parker M. Iqbal 
Published: February 2006

AbstractThe effects of cyclophosphamide (CPA), administered to pregnant inbred CBA/Ca mice 60 h after copulation, on cell number, mitotic index, chromosome structure, histone synthesis, and DNA synthesis of 84‐h blastocysts, and the subsequent development of these blastocysts cultured for a further 120 h in vitro are described. Cyclophosphamide 4, 20, and 40 mg/kg significantly increased the number of chromosomally aberrant cells, chromosomal aberrations, and chromosome breaks in the blastocysts. Chromosomal rearrangements were significantly increased in the CPA 20 and 40‐mg/kg treated groups, and in the 40‐mg/kg group the number of cells with ring chromosomes was significantly increased. Histone synthesis and DNA synthesis were significantly inhibited in the CPA 20 and 40‐mg/kg treated groups. Blastocyst cell number in each of the treated groups was less than the controls. On subsequent culture in vitro, significantly fewer embryos in the CPA 20 and 40‐mg/kg groups hatched, attached, developed trophoblast outgrowths, and expanded their inner cell masses. However, the differentiation of inner cell mass into ectoderm and endoderm was impaired by all three doses of the drug. These results demonstrate that CPA administered to pregnant mice 60 h after copulation has a clastogenic effect and interferes with synthesis of DNA and histones in the preimplantation embryo, and that the drug inhibits the subsequent development and differentiation of these embryos. Cytogenetic analysis of preimplantation embryos might be a useful adjunct to the existing methods in the evaluation of the embryotoxicity of drugs and chemicals.