bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of glass bead packing on the fibrillation of liquid‐crystalline polymer in polycarbonate
Authors: Chen Peng , Chen Jun , Zhang Baoqing , Zhang Jun , He Jiasong 
Published: February 2006

AbstractPolycarbonate (PC) was melt blended with small amount of liquid‐crystalline polymer (LCP) and various contents of glass beads (GB) having different diameters. The rheological measurements indicated that the GB addition increased the viscosity ratio and seemed unfavorable to the LCP fibrillation. However, the morphological observation showed that the LCP fibrillation was promoted by the GB addition and varied with the GB packing. With the increased GB packing by increasing the GB content and/or decreasing the GB diameter, LCP deformed from spheres and ellipsoids into stretched ellipsoids at lower shear rates and into long fibrils at higher shear rates. Although higher content of smaller GB jammed into the larger LCP droplets and inhibited the LCP fibrillation, very long LCP fibrils formed at higher shear rates at a high enough packing of GB. The relationship between GB packing and LCP fibrillation revealed two kinds of hydrodynamic effects of GB promoting the LCP fibrillation: at lower GB packing, the shear flow was enhanced by the high local shear between GB, in quantity; and for a high enough GB packing, the shear flow was changed, in quality, into elongational flow, which was more effective for the LCP fibrillation. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1020–1030, 2006
Predicting the three‐dimensional structure of human P‐glycoprotein in absence of ATP by computational techniques embodying crosslinking data: Insight into the mechanism of ligand migration and binding sites
Authors: Vandevuer Stéphane , Van Bambeke Françoise , Tulkens Paul M. , Prévost Martine 
Published: February 2006

AbstractP‐glycoprotein is a membrane protein involved in the phenomenon of multidrug resistance. Its activity and transport function have been largely characterized by various biochemical studies and a low‐resolution image has been obtained by electron microscopy. Obtaining a high‐resolution structure is, however, still remote due to the inherent difficulties in the experimental determination of membrane protein structures. We present here a three‐dimensional (3D) atomic model of P‐glycoprotein in absence of ATP. This model was obtained using a combination of computational techniques including comparative modeling and rigid body dynamics simulations that embody all available cysteine disulfide crosslinking data characterizing the whole protein in absence of ATP. The model features rather well most of the experimental interresidue distances derived both in the transmembrane domains and in the nucleotide binding domains. The model is also in good agreement with electron microscopy data, particularly in terms of size and topology. It features a large cavity detected in the protein core into which seven ligands were successfully docked. Their predicted affinity correlates well with experimental values. Locations of docked ligands compare favorably with those suggested by cysteine‐scanning data. The finding of different positions both for a single ligand and for different ligands corroborates the experimental evidence indicating the existence of multiple drug binding sites. The interactions identified between P‐glycoprotein and the docked ligands reveal that different types of interactions such as H‐bonds, π–π and cation–π interactions occur in agreement with a recently proposed pharmacophore model of P‐glycoprotein ligands. Furthermore, the model also displays a lateral opening located in the transmembrane domains connecting the lipid bilayer to the central cavity. This feature supports rather well the commonly admitted mechanism of substrate uptake from the lipid bilayer. We propose that this 3D model may be an important tool to understand the structure–function relationship of P‐glycoprotein. Proteins 2006. © 2006 Wiley‐Liss, Inc.
In vitro testing of teratogenic agents using mammalian embryos
Authors: Kochhar D. M. 
Published: February 2006

AbstractThe need for efficient methods to screen new chemicals, drugs, and environmental pollutants for their teratogenic activity is obvious. The method currently available, ie, pregnant‐animal testing, is of considerable value but there are certain drawbacks which prevent reliance on this method alone as the predictive device. Nutritional state of the dam, variability in the developmental age of embryos from litter to litter and even within the same litter, metabolic differences between species, placental function, and a host of other factors must be taken into account before data obtained from animal testing can be logically extrapolated to human situation. Many of these variables are either eliminated altogether or at least can be controlled by the use of tissue culture techniques. After surveying a variety of in vitro systems, it is our opinion that organ culture, whole embryo culture, and a combination of the two offer at present the best potential for screening of suspected teratogens. These culture techniques provide a much better simulation of in vivo situations than isolated cells grown as monolayers. Among other advantages, these procedures allow one to exercise control over the effective concentration of the suspected teratogen to which an embryo is exposed and also the duration of this exposure. Since maternal metabolism or modification of the drug is routinely eliminated in these experiments, there is a need for exploring the use of drug‐metabolizing preparations as additives to the culture medium. The choice of limb bud in the screening system is promising since during its development, the limb progresses through a succession of embryonic processes that are generally relevant to other organ systems as well. Hence, such a screening system may not only predict teratogenicity but also provide insight into the mechanisms by which a test chemical is teratogenic.
A cell culture assay for tumor‐promoter‐dependent progression toward neoplastic phenotype: Detection of tumor promoters and promotion inhibitors
Authors: Colburn Nancy H. , Koehler Barbara A. , Nelson Katherine J. 
Published: February 2006

AbstractMouse epidermal cell lines have been identified which respond to tumor‐promoting (but not nonpromoting) phorbol esters with an irreversible shift in anchorage independence, an in vitro marker of neoplastic phenotype. This response may be analogous to a later stage of tumor promotion in vivo. The shift occurs at TPA concentrations as low as 0.1 ng/ml (1.6 × 10−10 M). The specificity of the soft agar growth response is not limited to phorbol esters but extends to nonphorbol plant diterpenes such as mezerein, to detergents, to polycyclic hydrocarbons present in cigarette smoke, and to some growth factors. All of the above classes of compounds have been previously shown to have tumor‐promoting and/or cocarcinogenic activity in mouse skin in vivo. Clonal heterogeneity for TPA responsiveness has been found. Clones which were highly responsive to phorbol esters were also highly responsive to other classes of promoters, indicating their usefulness both for promoter detection and mechanism studies. The anchorage‐independence response to TPA was inhibited by a series of retinoids whose activity paralleled that for inhibiting tumor promotion in vivo. Both retinoid inhibition and clonal heterogeneity for promoter response are being utilized to study determinants of preneoplastic progression.
Carcinogen–DNA interaction: Differential effects of distamycin‐A and spermine on the formation of 7‐methylguanine in DNA by N‐methyl‐N‐nitrosourea, methylmethanesulfonate, and dimethylsulfate
Authors: Rajalakshmi S. , Rao Prema M. , Sarma D. S. R. 
Published: February 2006

AbstractExperiments were designed to determine whether DNA conformation and sequence play any role in its methylation by N‐methyl‐N‐nitrosourea, methylmethanesulfonate, and dimethylsulfate, agents that are known to methylate DNA by different mechanisms but yield 7‐methylguanine as the major product. The approach taken was to bind ligands to DNA that interact with it stereospecifically and to study their effect on the formation of 7‐ methylguanine by the three methylating agents. The results indicate that both distamycin A and spermine shielded the formation of 7‐methylguanine in vitro in rat liver DNA by N‐methyl‐N‐nitrosourea but not by methylmethane‐sulfonate or dimethylsulfate; they did not, however, protect 2‐deoxyguanylic acid against methylation by N‐methyl‐N‐nitrosourea. Based on the mechanism by which the methylating agents and the ligands react with DNA, these results are interpreted to suggest that (1) guanines methylatable at the N‐7 position by N‐methyl‐N‐nitrosourea are located at, or close to, the binding sites of the ligands, probably the A‐T‐rich regions, and those methylatable by methyl‐ methanesulfonate and dimethylsulfate are distal to these regions, and/or (2) the conformation DNA assumes in the presence of distamycin A or spermine permits methylation by methylmethanesulfonate and dimethylsulfate but not by N‐methyl‐N‐nitrosourea. The study implicates DNA structure and/or its sequences in carcinogen‐DNA interaction.
Mutagenic activation of an antischistosomal drug by enteric streptococcus sps in vitro and in vivo
Authors: Molineaux C. J. , Batzinger R. P. , Schmidt W. , Bueding E. 
Published: February 2006

AbstractPrevious studies have shown that a new antischistosomal drug, 4‐isothiocyano‐4′‐nitro diphenylamine (CGP 4540, amoscanate), is not mutagenic in vitro, but the urines of animals treated with this drug have mutagenic activity. Mutagenicity can be eliminated by coadministration of some antibacterial agents and is not demonstrable in germ‐free animals. The present study describes attempts to isolate and identify intestinal microorganisms responsible for the mutagenic activation of amoscanate. Streptococcus equinus, isolated from the intestinal tract of mice, as well as some other species of Streptococcus, were found to produce mutagenic activation of amoscanate when introduced into animals pretreated with antibacterial agents. Similarly, incubation of these strains with amoscanate in vitro resulted in the formation of a mutagenic product.
Estimation of creatine phosphokinase and hydroxyproline in the developing limb: Its use in evaluating the effect of teratogens on myogenesis and chondrogenesis
Authors: Kwasigroch T. E. , Neubert D. 
Published: February 2006

AbstractForelimbs of mouse fetuses were examined for tissue‐specific, drug‐induced alterations in their biochemical composition. The activity of the enzyme creatine phosphokinase (CPK; to estimate myogenesis) and the content of hydroxyproline (HP; to estimate chondrogenesis) were compared in homogenates of control and treated mouse‐fetus forelimbs on day 14 of gestation. In addition, the content of DNA, RNA, and protein was also measured. Injection of 6‐aminonicotinamide (6‐AN) (15 mg/kg) on day 10 resulted in an overall growth retardation in day 14 fetuses and all biochemical parameters tested were reduced. The ratio of HP:CPK was unaffected by 6‐AN treatment. Retinoic acid (vitamin A acid; 100 mg/kg), administered to pregnant female mice on day 10, produced severe forelimb defects and resulted in a significant reduction in day 14 forelimb HP and RNA content, without altering CPK, DNA, or protein; thus, the HP:CPK ratio was decreased. These results indicated that (1) 6‐AN nonspecifically retards growth and cytodifferentiation in limbs; (2) retinoic acid inhibits synthesis of collagen and RNA; (3) retinoic acid has a differential effect upon chondrogenic and myogenic tissues of the limb, and (4) the comparison of HP content and CPK activity in tissue homogenates is an acceptable method of evaluating teratogenic compounds for selective effects.
Analysis of human spermatozoa for Y chromosomal nondisjunction
Authors: Kapp R. W. , Jacobson C. B. 
Published: February 2006

AbstractThe YFF sperm assay, which is a quantification of the incidence of sperm with two fluorescent bodies (YFF = two fluorescent bodies), was performed to measure Y chromosomal nondisjunction. Three categories of human sub‐ jects were analyzed: (1) nonexposed, (2) exposed to antineoplastic agents ‐ ie, chemo‐ and radiation therapy, and (3) dibromochloropropane (DBCP)‐exposed. The nonexposed individuals demonstrated a relatively constant mean YFF value of 1.3%, which was consistent with historical controls in this laboratory and with the results of other investigators. Further, a one‐way analysis of variance among the means of the control samples revealed no statistical differ‐ ences either between these men or within each man's samples. The individuals exposed to antineoplastic agents showed a three‐ to four‐fold increase in the incidence of YFF sperm three to six weeks after the initiation of exposure to Adriamycin® and X‐irradiation. The maximum percentages of YFF per 1,000 sperm for each individual in this exposed group were analyzed by Wilcoxon's distribution free rank sum test using a one‐sided alternative. The exposed individuals' maximum YFF percentages were statistically significantly increased when compared to the maximum YFF values of the non‐ exposed controls. The individuals exposed to the nematocide DBCP also exhibited a statistically significant increase in the number of sperm con‐ taining two Y chromosomes as determined by chi‐square analysis with one degree of freedom (P < 0.01).Data presented herein show statistically significant increases in the incidence of double Y chromosomes as measured by the presence of YFF sperm following exposure to Adriamycin®, X‐irradiation, and DBCP. It is suggested that men who have a history of antineoplastic therapy could be evaluated for evidence of Y‐Y nondisjunction with this method. In the event of an increased YFF sperm level, genetic counseling and amniocentesis should be made available to the spouse where pregnancy has occurred. Further, be‐ cause this procedure measures gametic mutation, is relatively simple, and is noninvasive, it should be considered for inclusion as part of a battery of medical tests for monitoring industrial populations.
Test of carcinogenicity of quercetin, a widely distributed mutagen in food
Authors: Saito Daizo , Shirai Atsuko , Matsushima Taijiro , Sugimura Takashi , Hirono Iwao 
Published: February 2006

AbstractThe carcinogenicity of quercetin, a flavonol, was tested in six‐week‐old ddY mice of both sexes. Groups of 38 males and 35 females were given pellet diet containing 2% quercetin throughout their life span. As controls, 16 males and 15 females were given basal diet. Animals in both test and control groups developed leukemia and tumors of the lung, forestomach, mammary gland, adrenal, and soft part tissues. In addition, some animals in groups treated with quercetin developed tumors of the heart, liver, salivary gland, ovary, and uterus. The incidences of these tumors in test and control groups were not statistically different.
Teratogenicity and embryotoxicity of nickel carbonyl in Syrian hamsters
Authors: Sunderma F. William , Shen Samuel K. , Reid Marilyn C. , Allpass Patricia R. 
Published: February 2006

AbstractNickel carbonyl was administered to groups of pregnant hamsters by inhalation (0.06 mg Ni(CO)4/liter/15 min) on days 4, 5, 6, 7, or 8 of gestation. The dams were killed on day 15 of gestation, and the fetuses were examined for malformations. Exposure to Ni(CO)4 on days 4 or 5 of gestation resulted in malformations in 5.5% (8/146) and 5.8% (10/171) of the progeny, respectively (P < 0.05, versus 0/95 in controls). The proportions of litters with malformed fetuses were 33% (4/12) and 24% (4/17) in dams exposed to Ni(CO)4 on days 4 and 5 of gestation (P < 0.05, versus 0/9 in litters of control dams). Progeny of dams exposed to Ni(CO)4 on days 4 and 5 included 9 fetuses with cystic lungs, 7 fetuses with exencephaly, 1 fetus with exencephaly plus fused rib, and 1 fetus with anophthalmia plus cleft palate. Hemorrhages into serous cavities were found in 18% (26/146) and 25% (42/171) of fetuses of dams exposed to Ni(CO)4 on days 4 or 5 of gestation. Such hemorrhages were not observed in controls. In progeny of dams exposed to Ni(CO)4 on days 6 or 7 of gestation, there was 1 fetus with fused ribs and there were 2 fetuses with hydronephrosis. In another experiment, pregnant hamsters were exposed to inhalation of Ni(CO)4 (0.06 mg/liter/15 min) on day 5 of gestation; these dams were permitted to deliver their litters and to nurse their pups. On the day of delivery, there was no significant difference in the average number of live pups in the Ni(CO)4‐exposed litters compared to control litters. Neonatal mortality was increased in Ni(CO)4‐exposed litters; by day 4 postpartum, the number of live pups averaged 7.6 ± 1.5 in Ni(CO)4‐exposed litters (P < 0.01 versus 9.6 ± 1.8 pups in control litters). This study demonstrates that Ni(CO)4 is teratogenic and embryotoxic in Syrian hamsters.
Detection of urinary metabolites of 2‐acetylaminofuorene by cultured hamster embryo cells and high performance liquid chromatography
Authors: Lebherz William B. , Shaikh Badaruddin , Pienta Roman J. 
Published: February 2006

AbstractUrine was collected from Sprague‐Dawley rats injected intraperitoneally with a suspension of 2‐acetylaminofluorene (AAF) or with an inert suspension vehicle. Morphological transformation was observed in clonal cultures of secondary passage hamster embryo cells (HEC) after the addition of AAF‐treated rat urine or concentrated urine extracts prepared by incubating the urine with β‐glucuronidase. No morphological alteration was observed in cultures treated with urine (or urine extracts) from rats injected with the suspension vehicle alone. The presence of N‐hydroxy‐ and ring‐hydroxylated metabolites of AAF in the AAF‐treated concentrated urine extract was confirmed by highperformance liquid chromatography (HPLC).
Mutagenicity of vinyl compounds in salmonella typhimurium
Authors: Lijinsky W. , Andrews A. W. 
Published: February 2006

AbstractEighteen compounds structurally related to the mutagenic carcinogen vinyl chloride have been tested for mutagenicity in five strains of Salmonella typhimurium. Acrolein, acrolein diethylacetal, acrylonitrile, allyl alcohol, allyl bromide, crotonaldehyde, crotyl alcohol, and vinyl bromide were mutagenic with one or more strains; acrolein bisulfite, acrolein oxime, acrylamide, acrylic acid, allylamine, trans‐cinnamaldehyde, trans‐cinnamic acid, crotonic acid, methyl methacrylate, and vinyl acetate were not mutagenic. The mutagenicity tests were performed both without and with activation by rat and hamster liver microsomal preparations (S9). All compounds were tested in the plate incorporation and/or liquid preincubation tests except vinyl bromide, which was tested as a gas.
Kinetics of uptake and biliary excretion of benzo(α)pyrene and mutagenic metabolites in isolated perfused rat liver
Authors: Forti G. Cantelli , Trieff N. M. 
Published: February 2006

AbstractAn isolated liver perfusion system was used as a simplifying tool to study the metabolism and excretion of benzo(α)pyrene (BP) as a prototype carcinogen/mutagen. Phenobarbital (PB) was used to induce liver microsomal enzymes in Sprague‐Dawley male rats prior to isolated liver perfusion. Control livers were run simultaneously using generally tritiated (G‐3 H)BP/BP as substrate in the perfusion medium. Both biliary excretion and liver weight were increased in the induced compared to control liver, but biliary flow when corrected for liver weight is statistically the same for both control and PB‐induced livers. The excretion rate of radioactivity in the bile is always higher for PB‐induced than for control liver (maximum radioactive excretion at 1 hr). There is a more rapid radioactivity removal in the liver perfusion medium for PB‐induced than for control livers. Data are explained by increased metabolism of BP in induced liver leading to the presence of more polar metabolites undergoing preferential biliary excretion than in the control liver. Results support in vivo experimental data. Extracts from liver and bile were tested for microbial mutagenicity by the Ames test (TA 100) after TLC separation. The control liver shows virtually no mutagenicity in bile, only in TLC fractions from the liver. The PB‐induced liver shows significant mutagenicity in several TLC fractions in both bile and liver. The net effect of induction is to produce more mutagenic metabolites of BP, excreted in the bile, and presenting a significant exposure of carcinogens/mutagens, and consequent hazard to man.
The mutagenicity of 45 nitrosamines in Salmonella typhimurium
Authors: Andrews A. W. , Lijinsky W. 
Published: February 2006

AbstractThe correlation between mutagenicity in the rat liver microsome–mediated Salmonella Mutagenicity Assay of Ames and carcinogenicity in rats was examined with three groups of nitrosamines. Qualitatively the correlation was good, but there was poor correlation between mutagenic potency and carcinogenic potency. Of 23 cyclic nitrosamines, 19 were carcinogenic and mutagenic, and two were carcinogenic but not mutagenic, and the carcinogenicity studies of the remaining two are not complete. Of six symmetrical aliphatic nitrosamines, five were carcinogenic and mutagenic while only one carcinogen was not mutagenic. The greatest discrepancy occurred among 16 asymmetric nitrosamines, where 11 were both carcinogenic and mutagenic, four were carcinogenic but nonmutagenic, and one carcinogenicity study is incomplete.
The Heritable Translocation Assay: Its relationship to assessment of genetic risk for future generations
Authors: Bishop Jack B. , Kodell Ralph L. 
Published: February 2006

AbstractThe Heritable Translocation Assay (HTA) is an in vivo mammalian mutation test which measures specific clastogenic damage. It can be subjected to rigorous statistical scrutiny and detects a type of heritable genetic damage that is known to contribute to the human disease burden. Because of these factors the HTA is one of the major tests of the battery used in regulatory evaluation of potential environmental mutagens. Although tests for detecting inherited translocations have been developed and improved over the past 40 years, further emphasis on several statistical considerations affecting the precision and reliability of HTA animal model data applied to regulatory hazard evaluation and risk assessment seems warranted. In this paper we have presented a brief history and the basic methodology for the HTA. Statistical concepts related to the design and implementation of HTA studies, such as the incorporation of false classification error probabilities in determination of required sample size and use of the single sample binomial versus Fisher's exact test for analysis of data, have been examined in detail. We have also suggested a simplified method of extrapolating HTA animal data to man similar to that used with carcinogenesis data and propose other developmental needs and perspectives for application of this assay to regulatory assessment of environmental mutagens.