bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation dose‐dependent variations of micronuclei production in cytochalasin B‐blocked human lymphocytes
Authors: Lee Tung‐Kwang , Wiley Albert L. , Esinhart James D. , Blackburn Lisa D. 
Published: February 2006

AbstractUsing the cytokinesis‐block technique, lymphocytes from healthy volunteers (n = 9) were evaluated for (1) the radiation dose‐response curve for micronuclei (MN) expression; (2) technique variables on the yield of MN; and (3) the shortest lymphocyte incubation time required for the MN assay. We found that the best fitting of relationships between increasing MN production and increasing irradiation dose (0–4.0 Gy) was the linear‐quadratic model as expressed by the yield equation Y = C + αD + βD2 (P = 0.0003). When lymphocytes were irradiated in vitro with 2.0 Gy and harvested at various time intervals, MN increased during the entire 84 hr culture time. The radiation caused a division delay in lymphocyte as indicated by an increased frequency of mononucleated cells and a decreased number of mitotic indices. The data showed that a shortened culture time (60 hr) for the MN assay is possible and that binucleated cells with ⩾ 3 MN were found only in cells irradiated at ⩾ 2.0 Gy. These findings suggest that scoring of MN in lymphocytes may be a practical biological dosimeter for the rapid screening of accidental radiation exposure victims, especially when their clinical manifestations are not obvious. © 1994 Wiley‐Liss, Inc.
Congenital malformations in the offspring of male mice treated with ethylnitrosourea at the embryonic stage
Authors: Wada Azusa , Sato Masako , Takashima Hiromasa , Nagao Tetsuji 
Published: February 2006

AbstractEthylnitrosourea (ENU) was i.p. injected into ICR female mice at 25 or 50 mg/kg on day 10 of gestation, and male newborns treated with ENU at the embryonic stage were obtained. The treated males were aged for 10 weeks and then mated to untreated females of the same strain. The male germ cells used in the copulation correspond to primordial germ cells (PGC) at the time of ENU treatment. The F1 offspring were sampled as fetuses on day 18 of gestation and inspected for external and skeletal malformations. Evidence of F1 teratogenesis due to the mutagenized PGC was obtained when the fetuses from the males treated with 25 mg ENU/kg were inspected the frequencies of skeletally malformed fetuses in the ENU‐treated series and the control being, respectively, 1.0% (14/1,360) and 0.3% (3/1,017). The fetuses from 50 mg/kg‐treated males did not show a significant increase in malformations, most probably reflecting a high vulnerability of PGC to the killing effect of ENU. The findings in this study suggest that germ cell stage at PGC is at risk for the induction of congenital malformations by environmental chemicals. © 1994 Wiley‐Liss, Inc.
Comparison of dexamethasone‐induced embryotoxicity in vitro in mouse and rat embryos
Authors: Hansen Deborah K. , Grafton Thomas F. 
Published: February 2006

AbstractPrevious work demonstrated that rat embryos were more susceptible to the growth retardation effect of the synthetic glucocorticoid dexamethasone (DEX) in vivo than were mouse embryos. The purpose of this study was to examine this species difference using an in vitro system. Embryos of CD rats and CD‐1 mice were cultured in a whole embryo culture system with concentrations of DEX from 5 to 250 μg/ml. Rat embryos were explanted on day 9 of gestation (GD 9: plug day = GD 0), while mouse embryos were removed on GD 8. After 48 h in culture, each viable embryo was evaluated for morphological score, and the number of somite pairs, crown‐rump, and head lengths, as well as DNA and protein concentrations were determined. A reduced morphological score was observed for mouse embryos at 5 μg DEX/ml, but a significant decrease in this parameter was only observed at DEX concentrations of ⩾ 100 μg/ml in rat embryos. Significant reductions in the number of somite pairs were observed at 25 μg/ml for mouse embryos and 100 μg/ml for rat embryos. Crown‐rump and head lengths as well as DNA and protein concentrations were significantly decreased at 100 μg/ml in mouse embryos and 150 μg/ml in rat embryos. Therefore, in vitro mouse embryos were adversely affected by lower concentrations of DEX than were rat embryos for each of the six end points examined in this study. This species sensitivity in vitro could be due to inherent genetic differences or to the slightly different developmental stages evaluated using the culture system. The species sensitivity observed in vivo may be due to a maternal difference in the pharmacodynamics of the drug. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as suh, is in the public domain in the United States of America.
Differences in teratogenic and toxic properties of alcohol dehydrogenase inhibitors pyrazole and 4‐methylpyrazole in Drosophila melanogaster. II. ADH allozymes in an isogenic background
Authors: Eisses Karel Th. 
Published: February 2006

AbstractPyrazole and 4‐methylpyrazole (4‐MP) are in vivo and in vitro inhibitors of alcohol dehydrogenase activity in mammals. The fruitfly Drosophila melanogaster has been used to demonstrate the influence of genetic variation in alcohol dehydrogenase alleles on the results of larval treatment with pyrazole and 4‐MP. Genetic polymorphism of organisms involved in experiments with teratogenic and toxic agents is not often considered. Administration of pyrazole to larvae of isogenic D. melanogaster strains, differing mainly in their Adh alleles, caused large Notch‐like teratogenic aberrations, macrochaetae multiplication, and pupal mortality. The level of teratogenicity and developmental‐toxicity of pyrazole was both concentration and Adh‐genotype‐dependent. The strain with the highest ADH activity showed smaller effects after the treatments with the two concentrations used. 4‐MP does not cause morphological aberrations, although treatment of larvae with an isogenic background caused a high pupal mortality due to non‐differentiated material in the pupal case. © 1994 Wiley‐Liss, Inc.
Measurement of DNA integrity and structure in Xenopus embryos in the presence of hydroxyurea, actinomycin‐D, and triethylenemelamine using the fluorescent probe hoechst 33258
Authors: Stringer Bradley K. , Blankemeyer James T. 
Published: February 2006

AbstractCell health assay of water quality (CHAWQ) is an assay using intracellular biomarkers measured by optical techniques. CHAWQ uses embryos of the South African clawed frog, Xenopus laevis, and optical transducers of intracellular biomarkers to obtain rapid assessment of toxicity to frog embryos. Since the biomarkers are common to all cells, CHAWQ can indicate toxicity of different classes of chemicals. Among the biomarkers used are (1) the change in synthesis rate, (2) the structure, or (3) the environment of DNA. Measurement of DNA to detect genotoxicants has previously used extracted DNA or flow cytometry to detect alterations in DNA content or configuration. We report the use of viable frog embryos and the fluorescent probe Hoechst 33258 to detect the effect of three DNA‐active chemicals—actinomycin‐D, hydroxyurea, and triethylenemelamine (TEM)—on DNA in intact embryos. We found that we can detect changes in the DNA in the presence of toxicants at concentrations comparable to longer‐term assays but following a much shorter time of drug exposure. Actinomycin‐D caused a fluorescence decrease, TEM caused a fluorescence increase, whereas hydroxyurea gave a biphasic response. Hydroxyurea caused a decrease at low concentrations and an increase at higher concentrations. Concentration‐response data for TEM, hydroxyurea, and actinomycin‐D generated EC50 values of 0.1 mg/ml, 1.4 mg/ml, and 6.34 μg/ml, respectively. © 1995 Wiley‐Liss, Inc.
Embryotoxicity induced by alkylating agents: 9. Low dose prenatal‐toxic risk estimation of ethylmethanesulfonate based on No‐observed‐adverse‐effect‐level risk factor approach, dose‐response relationships, and molecular dosimetry
Authors: Platzek Thomas , Bochert Gerd , Meister Reinhard 
Published: February 2006

AbstractAnalogously to an earlier study using methylnitrosourea (MNU) the prenatal‐toxic risk of low doses of ethylmethanesulfonate (EMS) was estimated using different procedures, comparatively. First, the risk of low doses was estimated using linear extrapolation to zero. When using the variable “all gross structural abnormalities” the lowest effective dose in the experiment was 150 mg/kg body wt (5.6% incidence), the additional risk over background was calculated to be 5.0%, and the hypothetical incidence 0.1% was associated with the dose 3 mg/kg EMS. When evaluating “gross structural limb abnormalities,” which are not observed in controls, the dose associated with the hypothetical incidence 0.1% was 17.4 mg/kg EMS.Furthermore, derived from a dose‐response study of teratogenicity extrapolation to the possible risk of low doses was performed using nonlinear mathematical models. In this case, the results obtained are dependent on the dose response variable as well as from the statistical approach which was chosen. As an example, the values obtained from one evaluation are given: all gross structural abnormalities, Weibull transformation, jackknife approach: ED0.1% = 72 mg/kg EMS.For comparison a “virtually safe dose” was calculated by use of the no‐observed‐adverse‐effect‐level (NOAEL) risk factor approach. The NOAEL under our experimental conditions was 100 mg per kg body wt. By using an arbitrarily chosen risk factor of 100 a “safe dose” of 1 mg EMS per kg body wt was obtained.In addition, molecular dosimetry of the DNA adduct rate of O6‐ethylguanine in the 11‐day‐old embryos was used. Based on the assumption that a linear correlation exists between this specific adduct rate and the incidence of teratogenic effects, the hypothetical incidence of 0.1% was associated with a dose of 99 mg/kg EMS. This value is quite similar to that obtained by extrapolation using probit analysis which is in contrast to the results obtained with MNU. © 1995 Wiley‐Liss, Inc.
2‐aminofluorene bioactivation by human term placental peroxidase
Authors: Murthy K. R. , Joseph P. , Kulkarni Arun P. 
Published: February 2006

AbstractEarlier investigations from our laboratory demonstrated that human term placental peroxidase (HTPP) is capable of metabolism of xenobiotics and endogenous compounds. In this study, purified HTPP was found to bioactivate 2‐aminofluorene (2‐AF) in the presence of H2O2. 2‐AF oxidation was studied spectrophotometrically while radiometry was employed to assess the bioactivation. The rate of oxidation and covalent binding to protein and DNA was dependent upon the pH of the reaction medium and the concentration of 2‐AF, the enzyme, and H2O2. To observe maximal enzyme velocity of oxidation, the presence of 16.5 μM H2O2, 100 μM 2‐AF, 37 γg of the enzyme protein/ml, and pH 7.2 was required. Under optimal assay conditions, the range of specific activity between 130 and 165 nmol of 2‐AF oxidized/min/mg HTPP was observed. Using similar assay conditions, the magnitude of covalent binding of [3H]‐2‐AF to protein (BSA) and calf thymus DNA was found to be about 508 pmol bound/min/mg HTPP/mg BSA and 84 pmol bound/min/mg HTPP/mg DNA, respectively. Potassium cyanide and sodium azide, the known inhibitors of different peroxidases, significantly blocked both the oxidation and covalent binding of 2‐AF in a dose dependent manner. These results strongly suggest that peroxidase may be one of the important pathways responsible for the bioactivation of arylamines in human term placenta. © 1995 Wiley‐Liss, Inc.
Modulatory influence of arecanut on the mouse hepatic xenobiotic detoxication system and skin papillomagenesis
Authors: Singh Anjali , Rao A. R. 
Published: February 2006

AbstractThe modulatory influence of arecanut, a masticatory in several human populations, on the levels of biotransformation system enzymes in mouse liver has been studied. Swiss albino mice of either sex (4 weeks old) were fed on diets containing 0.25%, 0.5%, or 1% arecanut (w/w) for 5 weeks. In addition, a group of mice received a 1% arecanut diet for 36 weeks. The findings revealed a significant increase in hepatic levels of cytochrome b5, cytochrome P‐450, malondialdehyde (MDA), and glutathione S‐transferase (GST). The hepatic –SH content was depressed by 0.5% and 1% arecanut diets. Long‐term feeding of a 1% arecanut diet elicited changes similar to those seen following treatment for 5 weeks. Arecanut‐modulated profiles of biotransformation enzymes and antioxidant levels are suggestive of its influence in the process of carcinogenesis induced by bioactivated electrophilic species of potential chemical carcinogens among habitual arecanut chewers. Arecanut was also tested for its potency either to induce or to alter 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced papillomagenesis in the skin of the mouse. Animals put on a 1% arecanut diet and treated with a standard two‐stage protocol for tumor induction developed a 5.41 tumor burden (control value: 5.76) along with 100% incidence of mice bearing papillomas (control value: 94.4%), thus signifying that dietary intake of 1% arecanut for 18 weeks could not induce/alter the mouse skin tumorigenesis pattern. © 1995 Wiley‐Liss, Inc.
Covalent binding of carbon tetrachloride reactive metabolites to liver microsomal and nuclear lipid and phospholipid classes from sprague dawley and osborne mendel male rats
Authors: Fanelli S. L. , Castro J. A. 
Published: February 2006

AbstractThe interaction between carbon tetrachloride (CCl4)‐reactive metabolites and liver microsomal or nuclear lipids (covalent binding = CB) was studied in male rats from Osborne Mendel (OM) and Sprague Dawley (SD), strains with different cancer susceptibility. The in vitro or in vivo CB was more intense in OM than in SD.Most of the CB was with phospholipid (PL; SD > OM). The CB to cholesterol (CH) and cholesterol esters (CHE) was OM > SD. We also observed the presence of specific adducts only present in lipids from either OM or SD strains.The results were related to the well‐known role of PL and CH derivatives in gene function control and cell growth. © 1995 Wiley‐Liss, Inc.
Susceptibility to vinblastine‐induced aneuploidy and preferential chromosome segregation during meiosis I in Robertsonian heterozygous mice
Authors: Pacchierotti Francesca , Tiveron Cecilia , Mailhes John B. , Davisson Muriel T. 
Published: February 2006

AbstractChromosome segregation at meiosis I was studied in oocytes and spermatocytes of four different Robertsonian (Rb) heterozygous mouse stocks by cytogenetic analysis of meiotic products. Two Rb heterozygotes spontaneously yielded high frequencies of unbalanced oocytes. In one case, Rb(2.18)Rma, the excess hyperploidy was mainly accounted for by nondisjunction of normal bivalents, suggesting a generalized impairment of meiotic segregation. In each stock, frequencies of hyperploid spermatocytes were either not significantly different or significantly lower than the corresponding frequencies in the oocytes. This confirmed the greater risk of segregational errors in female than in male carriers of the same Rb metacentric. The hypothesis that an error prone system of meiotic segregation, such as the trivalent configuration of single Rb heterozygous oocytes, could be hypersensitive to chemically induced malsegregation was tested by injecting Rb heterozygous females with low doses of vinblastine (VBL). An intraperitoneal injection of 0.06 or 0.09 mg/kg VBL before the first meiotic division significantly increased the spontaneous frequency of hyperploid oocytes, inducing segregational errors of both the trivalent and normal bivalents. The comparison of these data with VBL effects in B6C3F1 mice showed that single Rb heterozygous oocytes are more sensitive to VBL‐induced meiotic aneuploidy than oocytes with a standard karyotype.Although segregation distortion has been repeatedly shown in the progeny of Rb heterozygous mice with a significant excess of all telocentric balanced offspring, it has never been demonstrated whether this is a primary event occurring during meiotic segregation or a consequence of selective postconceptional death. In this study, we showed that preferential segregation occurred during female meiosis in all the Rb stocks tested. When segregation distortion was analyzed separately in balanced and unbalanced oocytes, the latter did not show preferential segregation, suggesting that, when the two telocentrics segregated from each other, then the metacentric was randomly directed to the ovum or the polar body © 1996 Wiley‐Liss, Inc.
Mouse embryonic development and tumor cell growth under the influence of recombinant trichosanthin (a ribosome inactivating protein) and its muteins
Authors: Chan W. Y. , Ng T. B. , Shaw P. C. 
Published: February 2006

AbstractTrichosanthin, a ribosome inactivating protein, is known to possess embryotoxic and antiproliferative activities. In the present study recombinant trichosanthin and its muteins produced by site‐directed mutagenesis were tested for these activities using whole embryo culture and cell culture. The results revealed that when Glu 160 in trichosanthin was mutated to alanine or aspartate, the two aforementioned activities underwent a substantial decrease. However, the former mutein had a higher potency than the latter mutein. When both Glu 160 and Glu 189 were mutated, the resultant mutant possessed very low antiproliferative and yet considerable embryotoxic activity, indicating the contribution from other amino acids in stabilizing the transition state complex of trichosanthin © 1996 Wiley‐Liss, Inc.
Chronic Feeding Study of deoxynivalenol in B6C3F1 male and female mice
Authors: Iverson Frank , Armstrong Cheryl , Nera Eduardo , Truelove John , Fernie Susan , Scott Peter , Stapley Robert , Hayward Stephen , Gunner Sol 
Published: February 2006

AbstractA 2 year feeding study was conducted with male and female B6C3F1 mice that consumed diets containing 0, 1, 5, or 10 ppm deoxynivalenol (DON). Survivability was good and, while the test animals gained less weight with increasing levels of DON in the diet, there were no consistent toxic manifestations associated with DON consumption. There was some evidence for an increase in serum IgA and IgG in females, and there were sporadic changes noted in the clinical chemistry and hematology parameters conducted at the terminal sacrifice. However, these changes were not considered to be biologically significant. The pathology results provided statistically significant dose‐related evidence for a decrease in liver preneoplastic and neoplastic lesions as the dose level of DON increased. This negative trend probably results from the known positive correlation between body weight and the appearance of spontaneous hepatic neoplasms in this strain of mouse. © 1996 Wiley‐Liss, Inc.
Neoplastic transformation by quartz in the BALB/3T3/A31‐1‐1 cell line and the effects of associated minerals
Authors: Saffiotti Umberto , Ahmed Nadera 
Published: February 2006

AbstractQuartz, the most common form of crystalline silica, was tested quantitatively for neoplastic transformation in the mouse embryo cell line, BALB/3T3/A31‐1‐1. Five quartz dust samples of respirable size [Min‐U‐Sil 5 (MQZ); hydrofluoric‐acid‐etched MQZ (HFMQZ); Chinese standard quartz (CSQZ); DQ12; and F600] all induced significant levels of neoplastic transformation, showing dose‐dependent increases in the frequency of morphologically transformed foci at lower tested doses and a plateau level of response at higher doses. The plateau levels reached by the five tested samples did not differ substantially (maximum transformation frequencies per 105 cells ranging from 53.2 for MQZ to 28.3 for HFMQZ). F600 had minimal cytotoxicity but transforming activity comparable to the other samples. Cells from all tested transformed foci, when injected s.c. in nude mice, grew as sarcomas. Cytogenetic analysis showed that all tested silica‐transformed cell lines had acquired one to five additional marker chromosomes, of types not seen in untreated control lines, indicative of induced chromosomal translocations and amplification. Increased expression of one or more of five genes (p53, myc, H‐ras, K‐ras, and abl) was observed in several quartz‐transformed cell lines. No transforming activity was found for hematite and anatase (both nontoxic), and for rutile (more toxic than MQZ). Combined exposure (1:1 w/w per unit culture area) of each of these dusts with MQZ showed that hematite and anatase inhibited MQZ toxicity as well as transformation, whereas rutile markedly enhanced MQZ toxicity but not MQZ‐induced transformation. © 1996 Wiley‐Liss, Inc.
Another brick in the wall? Recent developments concerning the yeast cell envelope
Authors: Stratford Malcolm 
Published: February 2006

AbstractTo a yeast, the cell wall is an important living organelle performing a number of vital functions, including osmotic and physical protection, selective permeability barrier, immobilized enzyme support and cell‐cell recognition and adhesion. Our basic model of wall structure involves attachment of secreted mannoproteins to a fibrillar inner layer of β‐glucan. Recent work has emphasised the importance of chitin in lateral walls, examined the mechanisms of attachment of mannoproteins to the various cell wall glucan fractions and elucidated the pathway of β‐glucan synthesis, by means of resistance to glucan‐binding killer toxins. The conventional view of wall structure has been challenged by the discovery of a class of GPI‐anchored, serine/threonine‐rich wall‐proteins. It has been suggested, that these proteins are anchored in the plasma membrane, spanning the wall with extended O‐glycosylated structures and protruding out into the medium. Examination of these proteins shows a diversity of structures, sizes and behaviour that makes it improbable that these represent a new class of wall proteins. The possible roles of one of these proteins associated with flocculation, Flo1p, are discussed.
Intact acute cardiorenal and humoral responsiveness following chronic subcutaneous administration of the cardiac peptide BNP in experimental heart failure
Authors: Chen Horng H. , Schirger John A. , Cataliotti Alessandro , Burnett John C. 
Published: February 2006

AbstractBackground:BNP is a cardiac peptide with vasodilating, lusitropic and natriuretic properties mediated by the second messenger cGMP. We have previously shown that chronic subcutaneous (SQ) administration of BNP in experimental CHF resulted in improved haemodynamics and unloading of the heart. However, it is unknown if this will lead to the development of tolerance to exogenous BNP.Methods:The current study extends our previous study and compares the cardiorenal effects of acute administration of SQ BNP (5 μg/kg) in a group of dogs (n = 5) with rapid ventricular pacing induced CHF (180 bpm for 10 days) to a separate group of CHF dogs (n = 6), who received chronic SQ BNP (5 μg/kg) three times a day for 10 days.Results:Acute administration of SQ BNP resulted in similar increases in both plasma cGMP (35 ± 5 vs. 29 + 2 pmol/ml) and urinary cGMP excretion (UcGMPV) (6000 ±1000 vs. 4000 ± 600 pmol/min) in both the Chronic SQ BNP treated and the Untreated CHF groups (P>0.05). These were associated with decreased cardiac filling pressures and increased urine flow, which were also similar in both groups.Conclusion:In experimental CHF, chronic SQ BNP administration did not result in the development of tolerance as demonstrated by increases in both plasma cGMP and UcGMPV following acute administration of SQ BNP. This may have important clinical implications, suggesting that chronic BNP administration does not lead to the development of tolerance to acute BNP administration.