bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium/calcium exchanger expression in the mouse and rat olfactory systems
Authors: Pyrski Martina , Koo Jae Hyung , Polumuri Swamy K. , Ruknudin Abdul M. , Margolis Joyce W. , Schulze Dan H. , Margolis Frank L.
Published: February 2007

Sodium/calcium (Na+/Ca2+) exchangers are membrane transport systems that regulate Ca2+‐homeostasis in many eukaryotic cells. In olfactory and vomeronasal sensory neurons ligand‐induced olfactory signal transduction is associated with influx and elevation of intracellular Ca2+, [Ca2+]i. While much effort has been devoted to the characterization of Ca2+‐related excitation and adaptation events of olfactory chemosensory neurons (OSNs), much less is known about mechanisms that return [Ca2+]i to the resting state. To identify proteins participating in the poststimulus Ca2+‐clearance of mouse OSNs, we analyzed the expression of three potassium (K+)‐independent (NCX1, 2, 3) and three K+‐dependent (NCKX1, 2, 3) Na+/Ca2+ exchangers. In situ hybridization showed that mRNAs of all six Na+/Ca2+ exchangers coexist in neurons of the olfactory and vomeronasal systems, and that some are already detectable in the embryo. Of these, NCX1 and NCKX1 represent the most and least abundant mRNAs, respectively. Moreover, immunohistochemistry revealed that the NCX1, 2, and 3 proteins are expressed in nearly all neurons of the olfactory epithelium, the vomeronasal organ, the septal organ of Masera, and the Grueneberg ganglion. These three exchanger proteins display different expression profiles in dendrites, knobs, and plasma membranes of OSNs and in sustentacular cells. Furthermore, we show that NCX1 mRNA in rat olfactory mucosa is expressed as 8 alternative splice variants. This is the first comprehensive analysis of Na+/Ca2+ exchanger expression in the mammalian olfactory system. Our results suggest that Ca2+‐extrusion by OSNs utilizes multiple different Na+/Ca2+ exchangers and that different subtypes are targeted to different subcellular compartments. J. Comp. Neurol. 501:944–958, 2007. © 2007 Wiley‐Liss, Inc.
Time course of cerebellar morphological development in postnatal ferrets: Ontogenetic and comparative perspectives
Authors: Christensson Maria , Broman Jonas , Garwicz Martin
Published: February 2007

We provide the first systematic description of the morphological ontogenesis of the ferret cerebellum and compare its relative time‐course to that of the rat cerebellum. Overall cerebellar size, foliation, and thickness of cortical layers were quantified and Purkinje cell morphology was characterized at 24 timepoints in ferrets from postnatal day (P)1 to P63. The ferret cerebellum was substantially larger than that of the rat and had a much longer developmental period. In ferrets, Purkinje cells were dispersed into a monolayer by P9, the formation of folia declined abruptly around P20, and the external granular layer peaked in thickness around P22 and disappeared by P56. Timepoints of corresponding relative developmental maturity of the quantified architectural features of rat and ferret cerebella were determined and their relationship was analyzed by linear regression. The time‐conversion equation derived, describing the relationship between cerebellar morphogenesis in the two species, had a determination coefficient (r2) of 0.95. Conspicuously, the equation predicted with high accuracy the timing of structural changes in individual Purkinje cells in the ferret cerebellum. The conversion equation should be useful for precise quantitative translation of data between studies of ferret and rat cerebellum and for comparisons between development of motor and sensory structures and functions in ferrets. The degree of similarity in the time‐courses of cerebellar development in two distantly related mammals makes explicit in quantitative terms how remarkably conserved the cerebellum is in phylogenesis. Therefore, the methodology should be applicable to precise quantitative conversions of cerebellar developmental time‐courses also between other species. J. Comp. Neurol. 501:916–930, 2007. © 2007 Wiley‐Liss, Inc.
Clone‐specific anti‐CD45 blocking factor in patient plasma
Authors: Wellhausen Samuel R. , Slone Stephen P. , Miller James J.
Published: February 2007

We observed inhibition of anti‐CD45, but not anti‐CD3, ‐CD4, or ‐CD8 staining in the whole blood of an individual clinical specimen. Subsequent experiments demonstrated the presence of a plasma factor, which likewise blocked CD45 staining of third party lymphocytes. The blocking activity was anti‐CD45 clone (2D1) specific. Experiments utilizing immunoabsorption, immunofluorescence, and commercial blocking reagents failed to provide evidence for identifying blocking factor as heterophilic antibody. Biochemical identification of blocking factor was not accomplished. © 2007 Clinical Cytometry Society.
Nachweis der Tragfähigkeit bei Zug‐ und Biegezugbeanspruchung nach DIN 1053‐100
Authors: Brameshuber Wolfgang , Schmidt Ulf
Published: February 2007

Der Nachweis der Zug‐ und Biegezugbeanspruchung wurde auf einen Kräfte‐Momentennachweis umgestellt. Grundlage für die Bestimmung der Tragkräfte bzw.‐momente sind charakteristische Zug‐ und Biegezugfestigkeiten. Der Ansatz der Zugfestigkeit senkrecht zur Lagerfuge ist nach wie vor nicht zulässig. In diesem Beitrag werden die Nachweise mit Hintergrundinformationen erläutert.
Differential effects of stress and amphetamine administration on Fos‐like protein expression in corticotropin releasing factor‐neurons of the rat brain
Authors: Rotllant David , Nadal Roser , Armario Antonio
Published: February 2007

Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine‐induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole‐board, HB) nor immobilization (IMO) increased Fos‐like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos‐like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Polarization and transverse mode control of vertical cavity surface emitting lasers with metal nano‐structure
Authors: Hashizume Jiro , Koyama Fumio
Published: February 2007

The surface emitting laser is one of the leading candidates for a light source supporting next‐generation ultrahigh‐speed optical linking techniques. However, in surface emitting lasers, especially for the single mode elements, the challenges include increasing the single mode output and stabilizing the polarization direction, and thus the technique for controlling the polarization and transverse modes is important. In this study, we propose a surface emitting laser with a metal nanoscale aperture array whose permeability shows a strong polarization dependence, formed on a p‐type semiconductor multilayered film reflector, as a new method for controlling the polarization and transverse modes, and in addition, we explain the potential of its polarization and transverse mode control. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(3): 49–56, 2007; Published online in Wiley InterScience (www.interscience.wiley. com). DOI 10.1002/ecjb.20261
Analysis of ring filter and its cascade synthesis method
Authors: Ishida Hitoshi , Araki Kiyomichi
Published: February 2007

A ring resonator filter with a stub (ring filter) has a band‐stop filter characteristic. The attenuation frequencies are at two symmetric locations with respect to the center frequency of the passband. If the range between these two attenuation frequencies is considered as the passband, the loss is low and the group delay is constant in the passband region. In the present paper, the condition of the ripple generation in the passband is derived for the ring filter. Further, the ripple frequencies under the ripple generation conditions are numerically obtained and compared with the measured results. Next, the passband group delay is analytically derived and compared with the measured value. Further, a method of cascading the ring filters is studied. It is found that the transfer function of the cascaded ring filter is expressed in terms of a rational function of the Richard variable$\Omega = j\tan \theta$. It is shown that a set of the characteristic impedances realizing the desired rational function can be inversely calculated. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(3): 9–16, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20298
Abnormality of electric field at a wedgelike edge of a conductor or a dielectric interface and methods for its relaxation
Authors: Kawamoto Tadashi , Takuma Tadasu
Published: February 2007

Abnormal electric field appears at a wedgelike edge of a conductor (electrode) or a dielectric interface, which usually becomes infinitely high. This paper analyzes the electric field near such an edge by the analytical variable separation method and by the numerical one of the charge simulation method. The analysis focuses on the special conditions where the electric field becomes zero at an edge. These conditions are important for the insulation design to suppress the discharge inception at such edges of conductors and dielectric interfaces. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 159(1): 1–8, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20280
Robust design of body slip angle observer for electric vehicles and its experimental demonstration
Authors: Aoki Yoshifumi , Hori Yoichi
Published: February 2007

Electric vehicles (EVs) are inherently suitable for two‐dimensional vehicle motion control. To utilize EV's advantages, body slip angle β and yaw rate γ play an important role. However, as sensors to measure β are very expensive, we need to estimate β from only variables to be measurable. In this paper, an improved estimation method for body slip angle β for EVs is proposed. This method is based on a linear observer using side acceleration ay as well as γ information. We especially considered the design of gain matrix and succeeded in exact and robust estimation. We performed experiments by UOT March II. This experimental vehicle driven by four in‐wheel motors was made for research on advanced control of EVs. Some experimental results are shown to verify the effectiveness of the proposed method. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 159(1): 80–86, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20339
High‐precision positioning control for hard disk drives: 1st report: High‐precision simulator using differential iteration method
Authors: Kawafuku Motohiro , Otsu Kazuhiro , Iwasaki Makoto , Hirai Hiromu , Kobayashi Masahito , Okuyama Atsushi
Published: February 2007

The paper proposes a high‐precision simulator for the following mode system design in hard disk drives (HDDs). The simulator is composed of two models: one is a precise mechanical plant which includes numerous high‐frequency vibration modes, and the other is a disturbance signal model which is separated into various disturbances. In the proposed approach, a differential iteration method is applied to identify the precise mechanical plant, providing accurate experimental model analyses. The effectiveness of the synthesized simulator was verified by the comparative studies for experiments and numerical simulations. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 159(1): 54–61, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20457
Novel quasi‐interpenetrating network/gold nanoparticles composite matrices for DNA sequencing by CE
Authors: Zhou Dan , Wang Yanmei , Zhang Wenlong , Yang Runmiao , Shi Ronghua
Published: February 2007

In order to further improve ssDNA sequencing performances using quasi‐interpenetrating network (quasi‐IPN) as a matrix composed of linear polyacrylamide (LPA) with lower viscosity‐average molecular mass (3.3 MDa) and poly(N,N‐dimethylacrylamide) (PDMA), gold nanoparticles (GNPs) were prepared and added into this quasi‐IPN to form polymer/metal composite sieving matrices. The studies of intrinsic viscosity and differential scanning calorimetry (DSC) on quasi‐IPN and quasi‐IPN/GNPs indicate that there were interactions between GNPs and polymer chains. The sequencing performances on ssDNA using quasi‐IPN and quasi‐IPN/GNPs (with different GNPs concentrations) as sieving matrices were studied and compared by CE at different temperatures. The results show that resolutions of quasi‐IPN/GNPs were higher than those of quasi‐IPN without GNPs and approximated those of quasi‐IPN composed of LPA with higher MW (6.5 MDa) and PDMA without GNPs in the bare fused‐silica capillaries. Furthermore, the sequencing time of quasi‐IPN/GNPs was shorter than that of quasi‐IPN under the same sequencing conditions. The influences of GNPs and sequencing temperature on the sequencing performances of ssDNA were also discussed. The separation reproducibility of quasi‐IPN/GNPs solution was excellent and its shelf life was more than 8 months.
The apparent decrease in thiotepa‐induced chromosome aberrations in human lymphocytes caused by an effect of WR2721 on the cell cycle as found by the definitively determined division method
Authors: Wolff Sheldon , Arutyunyan Rouben
Published: February 2007

Antimutagenic radioprotective compounds have been reported to decrease the yield of chemically induced chromosome aberrations even when administered long before the chemical mutagen thio‐TEPA. Because thio‐TEPA can induce aberrations in all parts of the cell cycle, it seemed likely that the apparent decrease in aberrations was the result of an effect of the antimutagen on the progression of cells through the cell cycle so that cells treated in the more sensitive stage would be scored. To test this possibility human lymphocytes were treated with the protective compound WR2721 and then thio‐TEPA. The cells were grown in the presence of 5‐bromodeoxyuridine, which allows the definitive determination of metaphases from cells that divided once, twice, or three times after treatment. The yield of aberrations observed in first division cells was the same whether or not the protector was present. A decrease in aberration yields appeared only in rapidly cycling cells that were in the second division at the time of fixation. Labeling experiments showed that in this rapidly dividing population fewer of the metaphase cells had been in G2 when thio‐TEPA was added. The results indicate that part of the decrease in aberration yields obtained by treatment with an antimutagen several hours before the addition of a mutagen is an artifact of cell selection.
The estimation of mutation rates when premeiotic events are involved
Authors: Engels William R.
Published: February 2007

When mutation or recombination events occur premeiotically, the distribution of exceptional individuals among the offspring will be “clustered” as opposed to binomial. Even though the exact nature of the clustering is usually unknown, unbiased methods for measuring mutation rate and determining the precision of these measurements are given to replace a biased method now frequently used. When clustering is pronounced, the unweighted average mutation rate is found to be a more efficient estimator than the usual average weighted by family size. Methods of statistical inference and optimal experimental design in the absence of specific knowledge of the mechanism of clustering are also discussed.
Mutagenicity of cross‐links and monoadducts of furocoumarins (psoralen and angelicin) induced by 360‐nm radiation in excision‐repair‐defective and radiation‐insensitive strains of saccharomyces cerevisiae
Authors: Grant E. L. , Von Borstel R. C. , Ashwood‐Smith M. J.
Published: February 2007

The furocoumarin psoralen can form both monoadducts and cross‐links with DNA when combined with 360‐nm radiation, whereas the analog angelicin can form monoadducts only. Psoralen plus 360‐nm radiation causes mutation induction with a slope of 2 (log‐log plot) for a radiation‐insensitive strain, whereas angelicin action with 360‐nm radiation displays a slope of unity. For a radiation‐sensitive mutant defective in the excision‐repair pathway, the actions of both angelicin and psoralen plus 360‐nm radiation exhibit one‐target kinetics, but at higher exposures psoralen plus 360‐nm radiation assumes a slope of 2. The excision‐repair‐defective strain is considerably more sensitive to the furocoumarins plus 360‐nm radiation than is the radiation‐insensitive strain, both for killing and mutation induction.

The simplest explanation for the data is that both cross‐links and monoadducts, formed by furocoumarins with DNA when exposed to 360‐nm radiation, are capable of inducing mutations, and that monoadducts are repaired 20 times more efficiently than cross‐links by the excision‐repair pathway.
The mutagenicity of dialkyl nitrosamines in the salmonella plate assay
Authors: Prival Michael J. , King Valerie D. , Sheldon Albert T.
Published: February 2007

N‐nitrosodimethylamine (DMN) is not mutagenic in the standard Salmonella plate incorporation assay (Ames test) in the presence of an in vitro metabolic activation system (S‐9) derived from rat liver. When the S‐9 was derived from Aroclor‐ or phenobarbital‐induced mouse or hamster liver or from uninduced hamster liver, mutagenic activity was observed. Increasing the amount of S‐9 above the usual maximum level of 50 μ1 per plate increased the mutagenic response. Similarly, the mutagenicity of N‐nitrosodiethylamine (DEN) and N‐nitrosodi(n‐butyl)amine (DBN) was greater in the presence of hamster liver S‐9 than when mouse or rat liver was used. Data are also presented indicating that the ability of rat liver S‐9 to mediate the mutagenic activity of DMN in the “preincubation” assay is due to the fact that the various components are present in this assay at several times the concentrations attained in the standard plate incorporation assay.
Mutagenicity of resin acids identified in pulp and paper mill effluents using the salmonella/mammalian‐microsome assay
Authors: Nestmann Earle R. , Lee E. G.‐H. , Mueller J. C. , Douglas George R.
Published: February 2007

Ten resin acids which have been identified as constituents of pulp and paper mill effluents have been examined for potential mutagenicity in the Salmonella/mammalian‐microsome assay. Only neoabietic acid has been found to be mutagenic. Neoabietic acid showed dose‐related increases in mutagenicity in strains TA1535, TA100, TA1538, and TA98, but not in strain TA1537. Metabolic activation with a preparation of Aroclor 1254‐induced liver homogenate (S9) slightly reduced the mutagenic responses. Negative responses were found for abietic acid, dehydroabietic acid, levopimaric acid, 7‐oxodehydroabietic acid, monochlorodehydroabietic acid, dichlorodehydroabietic acid, pimaric acid, isopimaric acid, and sandaracopimaric acid.
Mutagenic evaluation of nitroparaffins in the salmonella typhimurium/mammalian‐microsome test and the micronucleus test
Authors: Hite Mark , Skeggs Helen
Published: February 2007

Three nitroparaffins (nitroethane, 1‐nitropropane, and 2‐nitropropane) were studied in the Salmonella typhimurium/mammalian microsome (Ames) test, with and without microsomal activation systems. Nitroethane and 2‐nitropropane also were studied in an in vivo mutagenic (micronucleus) test. These studies were undertaken because these solvents are widely used in the chemical and pharmaceutical industries and 2‐nitropropane was reported to cause liver cancer in rats exposed by the inhalation route.

Neither nitroethane nor 1‐nitropropane was active in the Ames test with Salmonella tester‐strains TA1537, TA92, TA98, or TA100. However, 2‐nitropropane produced a significant increase in revertants in all of these tester strains, particularly strain TA100, where 3μl/plate doubled the number of revertants in the presence of microsomal enzymes. Negative results were obtained with both nitroethane and 2‐nitropropane in micronucleus tests. These studies have shown that 2‐nitropropane has the potential for causing point mutations in a microbial test system. However, this compound probably will not cause a chromosome mutation of the clastogenic type.
The effect of 2,4‐diaminotoluene and isomers of dinitrotoluene on unscheduled dna synthesis in primary rat hepatocytes
Authors: Bermudez Edilberto , Tillery Deborah , Butterworth Byron E.
Published: February 2007

The important industrial chemicals 2,4‐dinitrotoluene (DNT) and 2,4‐diaminotoluene (DAT) are hepatocarcinogens in rats. Technical grade DNT contains approximately 76% 2,4‐DNT, 19% 2,6‐DNT, and lesser amounts of the other isomers. The ability of 2,4‐DAT, technical grade 2,4‐DNT, and the purified isomers 2,3‐DNT, 2,4‐DNT, 2,5‐DNT, 2,6‐DNT, 3,4‐DNT, and 3,5‐DNT to damage the DNA of primary rat hepatocytes was examined. Male Fischer‐344 rats were perfused in situ, single cell suspensions were obtained after liver dissociation, and cultures of these cells were treated in the presence of 3H‐thymidine. Autoradiography was employed to visualize label incorporation following repair of DNA. At the nontoxic (as judged by cell morphology) doses of 1 × 10−4 M and below, only 2,4‐DAT induced a significant response (ie an average greater than 5 grains net/nucleus). The activity seen with 2,4‐DAT suggests that damage to the DNA of the hepatocytes may play a role in its carcinogenic activity and is consistent with the proposal that the induction of DNA repair in primary hepatocytes is of value in predicting the activity of aromatic amino compounds. However, the carcinogenic activity of the dinitrotoluenes was not reflected as DNA repair in the isolated hepatocyte, indicating that additional factors involving the whole animal also play a role in the mechanism of action of DNT.
Mutagenic effects of bleomycin in drosophila melanogaster
Authors: Traut H.
Published: February 2007

Although bleomycin (BLM) induces structural chromosome damage, eg, in human lymphocytes, no, or at best a weak, mutagenicity of this substance has been observed after the application of two well‐established mutagenicity screening procedures, the Ames test and the sister‐chromatid exchange (SCE) test. After feeding BLM to Drosophila melanogaster males we, too, observed only a weak mutagenicity as measured by the frequency of recessive sex‐linked lethal mutations. These results are based on the analysis of postmeiotic germ cell stages (spermatozoa, spermatids). No autosomal translocations were found in the same experiments. BLM was also fed to Drosophila females under conditions similar or identical to those of the experiments with males. We observed a considerable sensitivity of Drosophila oocytes to the induction by BLM of recessive sex‐linked lethal mutations and X‐chromosomal aneuploidy (nondisjunction and chromosome loss). Our oocyte results demonstrate that the extensively used antitumor agent bleomycin has to be considered as mutagenic.
Sister chromatid exchange studies in human fibroblast—rat hepatocyte co‐cultures: A new in vitro system to study sces
Authors: Kligerman Andrew D. , Strom Stephen C. , Michalopoulos George
Published: February 2007

To approximate better the metabolic reactions that take place in vivo yet maintain the simplicity and reproducibility of in vitro systems, we have developed a co‐culture system making use of freshly isolated rat hepatocytes and confluent human fibroblasts for the study of SCE induction by genotoxic agents. Hepatocytes were obtained from male rats by reverse collagenase perfusion and plated over low‐passage male human fibroblasts. Preliminary studies demonstrated that although the number of hepatocytes plated was not critical, the best attachment to, and coverage of, the fibroblasts occurred when between 10 × 106 and 20 × 106 hepatocytes were plated/100 mm tissue culture dish. Results with the promutagen cyciophosphamide showed that the hepatocytes could metabolize the compound and deliver active moieties to the fibroblasts resulting in a linear dose‐dependent increase in SCE frequencies. Control fibroblast cultures lacking hepatocytes displayed no increase in SCE frequencies following cyclophosphamide administration.
Hyperthermia induced dissociation of the X‐Y bivalent in mice
Authors: Garriott M. L. , Chrisman C. L.
Published: February 2007

The mutagenic potential of hyperthermia was examined employing a spermatocyte test on males heat stressed continuously for 2, 3, or 5 days. Stress conditions were 35 ± 1° C and 65 ± 3% relative humidity. Males were sacrificed and meiotic preparations made from the testes at various intervals following removal from the stress environment. In this way, chromosome damage could be monitored in all premeiotic and early prophase I stages of spermatogenesis. Results of this study revealed a significant increase in the incidence of X and Y univalents at metaphase I. The significance of this finding is discussed.
Genotoxic activity in microorganisms of tetryl, 1,3‐dinitrobenzene and 1,3,5‐trinitrobenzene
Authors: McGregor Douglas B. , Riach Colin G. , Hastwell Rowan M. , Dacre Jack C.
Published: February 2007

N‐Methyl‐N,2,4,6‐tetranitroaniline (tetryl), 1,3‐dinitrobenzene, and 1,3,5‐trinitrobenzene were subjected to DNA repair assays using the Escherichia coli W3110/polA+, p3478/polA− system, reverse mutation assays with His− Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100, and mitotic recombinogenic tests with the yeast Saccharomyces cerevisiae D5. Tests were carried out in the absence of an exogenous activation system and in tissue homogenate‐mediated assays using Aroclor 1254‐induced, male rat‐liver‐derived S9 mix.

Mutagenic activity of tetryl was demonstrated with S typhimurium strains TA1537, TA1538, TA98, and TA100. The responses were particularly strong in the absence of S9 mix. Tetryl also induced increases in recombinant numbers and frequencies in the S cerevisiae test without the S9 mix, but not in its presence.

1,3‐Dinitrobenzene was demonstrated to be a mutagen with S typhimurium strains TA1538, TA98, and TA100. Slight activity was also seen with TA1537. The S9 mix reduced the magnitude of the responses.

1,3,5‐Trinitrobenzene was also demonstrated to be mutagenic with S typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100. Again, the S9 mix reduced the magnitude of the responses.

In this segment of a programme initiated by military authorities, the genotoxic potential of three nitroaromatic compounds, which have found significant use in explosive preparations, has been demonstrated.

Twelve other compounds used in ordnance were not active in any of the test systems. These were octahydro‐1‐acetyl‐3,5,7‐trinitro‐S‐tetramine (SEX), hexahydro‐1,3‐dinitro‐5‐acetyl‐S‐triamine (TAX), ethyl centralite, 2‐nitrodiphenylamine, N‐nitrosodiphenylamine, diphenylamine, diethyleneglycoldinitrate, nitroguanidine, lead salicylate, lead resorcylate, red phosphorus, and zinc chloride.
The mutagenicity of dialkylaminoalkyl chlorides in a battery of short‐term assays
Authors: Thompson Christina Z. , Rinzel Sharon M. , Probst Gregory S. , McMahon Robert E.
Published: February 2007

Dialkylaminoalkyl chlorides, valuable chemical manufacturing intermediates, were evaluated for their mutagenicity in several short‐term assays: The concentration gradient bacterial mutagen assay, the Ames test, the L5178Y mouse lymphoma cell assay, and the hepatocyte primary culture‐DNA repair test. The dialkylaminoethyl chlorides were active in all test systems. The relative mutagenic potencies of the ethyl chlorides were similar in the bacterial tests and the L5178Y cell assay. The dialkylaminopropyl chlorides were weakly mutagenic in two Salmonella strains but were inactive in the other test systems.

The purpose of the test battery used in these studies is to generate data on a test compound which could be used to make a rational prediction of the carcinogenic potential of the compound in test animals. On this basis, the results with the dialkylaminoethyl compounds suggest that if these agents which can form the aziridinium ion were evaluated in in vivo tests there is a reasonable chance some would be found to be carcinogenic. Alternatively, the data on the dialkylaminopropyl chlorides indicate that they have a rather low carcinogenic potential.
Isolation and partial characterization of mutagen‐sensitive and DNA repair mutants of chinese hamster fibroblasts
Authors: Schultz Roger Alan , Trosko James E. , Chang Chia‐Cheng
Published: February 2007

Through a new approach, we have sought to isolate ultraviolet light (UV)‐sensitive and DNA repair mutant Chinese hamster fibroblasts. The procedure consisted of 1) mutation induction by 5‐bromodeoxyuridine (BrdU)‐blacklight and UV treatments; 2) incorporation of 3H‐thymidine in repair‐proficient cells at high temperature (38.5°C) following UV damage; 3) cold holding (4.0°C) of these cells to induce tritium killing; and 4) recovery and testing of repair‐deficient and UV‐sensitive cells which have survived and formed colonies at low temperature (34.0°C). In our initial attempt at this protocol, we isolated 72 surviving colonies from 2 × 107 cells plated for selection. Of the 72 colonies. 20 demonstrated potential interest and four were selected for extensive study. One, identified as UVs−7, is slightly more sensitive to UV, but not sensitive to X rays or N‐acetoxy‐2‐acetylaminofluorene (NAc‐AAF). The mutant exhibits a highly reduced level of unscheduled DNA synthesis (UDS), as compared to the parental line. Two additional lines, UVs−40 and UVs−44, are sensitive to UV, X ray, N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG), and NAc‐AAF, but exhibit normal UDS. A fourth line, UVr−23, has enhanced UDS, is resistant to UV, but exhibits no difference in sensitivity to X ray or NAc‐AAF. These mutants are all stable, and should be useful for the study of mammalian DNA repair processes and mechanisms of mutagenesis.
The mutation studies of mutagen‐sensitive and dna repair mutants of chinese hamster fibroblasts
Authors: Schultz Roger Alan , Chang Chia‐Cheng , Trosko James E.
Published: February 2007

We have previously reported the isolation and partial characterization of DNA repair and/or mutagen‐sensitive mutant Chinese hamster cell strains. Here we present the results of a detailed study of the ultraviolet light (UV)‐induced mutability of one of these strains, UVs−7, and provide preliminary mutability data on two additional lines, UVr−23 and UVs−40. UVs−7 is extremely deficient in unscheduled DNA synthesis (UDS) but only slightly more sensitive to UV than the parental line. When examined for the UV‐inducibility of mutants resistant to ouabain, 6‐thioguanine, or diphtheria toxin, UVs−7 was found to be hyper‐mutable at all three loci as compared to the parental line. The degree of hypermutability was not the same for any two loci. UVs−40, a highly UV‐sensitive strain, was also found to be hypermutable at the ouabain‐resistant (ouar) locus. UVr−23, which is UV‐resistant and more proficient at UDS than the parental line, appeared to exhibit a tendency toward hypomutability at both the ouabain(ouar) and 6‐thioguanine‐resistant (6TGr) loci. Further characterization of all these lines should aid in delineating mammalian mechanisms of DNA repair and mutagenesis.
Synergistic, additive, and antagonistic mutagenic responses to binary mixtures of benzo(a)pyrene and benzo(e)pyrene as detected by strains TA98 and TA100 in the salmonella/microsome assay
Authors: Hass Bruce S. , Brooks Emily E. , Schumann Karen E. , Dornfeld Suzanne S.
Published: February 2007

Binary mixtures of benzo(a)pyrene (B(a)P) and benzo(e)pyrene (B(e)P) produce synergistic mutagenic (comutagenic) responses in Salmonella typhimurium strain TA98 (a frameshift detector). The optimum enhancement (25 ×) was found at B(a)P concentration of 0.3 μg/plate and B(e)P concentration of 1.5 μg/plate. The response of strain TA100 (mostly a base‐substitution detector) is opposite that of TA98, showing antagonism and additivity in similar concentration ranges.
A rapid and simple scheme for confirmation of salmonella tester strain phenotype
Authors: Zeiger Errol , Pagano Dennis A. , Robertson Iain G. C.
Published: February 2007

A simple scheme has been developed for confirming the phenotype of the standard set of Salmonella typhimurium tester strains. This scheme employs a series of filter paper discs impregnated with diagnostic mutagens or bacterial toxins. Up to 6 diagnostic discs can be placed on a petri dish to test a single Salmonella strain. The Salmonellae are distinguished by their responses to ampicillin, crystal violet, nitrofurantoin, 9‐aminoacridine, 4‐nitro‐o‐phenylenediamine and sodium azide.
Cytogenetic effects of cis‐platinum(II)diamminedichloride in vivo
Authors: Morrison William D. , Huff Vicki , Colyer Shirley P. , Dufrain Russell J. , Littlefield L. Gayle
Published: February 2007

The chemotherapeutic agent cis‐platinum(II)diamminedichloride (cis‐PDD) has been shown to be mutagenic, teratogenic, and carcinogenic. We determined the cytogenetic effects of cis‐PDD on human and rabbit lymphocytes in vitro and on rabbit marrow cells, lymph node cells, and lymphocytes in vivo. Lymphocyte cultures from two humans and one rabbit were treated in vitro with cis‐PDD. For in vivo studies, five New Zealand white rabbits were given iv injections of cis‐PDD. Posttreatment blood samples were withdrawn for analysis and rabbits were sacrificed at either 6 or 24 hr for cytogenetic analysis of marrow and node cells. Sister chromatid exchange (SCE) analysis of human and rabbit metaphases from lymphocytes treated in vitro showed that rabbit lymphocytes are more sensitive to SCE induction by cis‐PDD. Significant increases in SCE were observed in lymphocyte cultures obtained as early as 1 hr post treatment from injected rabbits. Analysis of node, marrow, and lymphocyte metaphases from injected rabbits showed a high number of chromosome aberrations in these cells with bone marrow showing a delayed response to treatment. These results indicate that cis‐PDD is clastogenic in hematopoietic tissues in vivo and that SCE methodology may be useful in monitoring patients receiving cis‐PDD therapy.
Aneuploidy patterns in drosophila melanogaster
Authors: Traut H.
Published: February 2007

By using an appropriate scheme, various combinations of losses and gains of chromosomes I and II arising in oocytes of Drosophila melanogaster were obtained. The frequencies of these combinations can be arranged as special sequences or patterns which we call “aneuploidy patterns.” Aneuploidy patterns were established for spontaneous, colchicine‐induced, and X‐ray=induced exceptions and were shown to be highly specific for the agent tested. Such patterns can be obtained very quickly, because only exceptional progeny survive. By establishing aneuploidy patterns for chemical agents one would get information on the “aneuploidizing” action of the compounds tested.
Diethylstilbestrol‐diphosphate induces chromosomal aberrations but not sister chromatid exchanges in murine bone marrow cells in vivo
Authors: Ivett J. L. , Tice R. R.
Published: February 2007

Diethylstilbestrol diphosphate (DES‐dp) clastogenesis was examined in the bone marrow of C57B1/6 male and female mice. Significant and sex‐related dose effects were observed for the induction of chromatid‐type chromosomal aberrations and for the inhibition of cellular proliferation. Females were more sensitive to the effects of DES‐dp than males when assessed for either induced chromosomal aberrations or proliferative inhibition. Contrary to other published results, we did not observe either an increase in sister chromatid exchanges or an increased incidence of aneuploidy. Ovariectomy reduced the ability of DES‐dp to inhibit cellular proliferation and decreased the high degree of variability between animals at high doses of DES‐dp. The results of our studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.
Herpes virus inactivation by chemical carcinogens: Differential inactivation of herpes simplex viruses by 4‐nitroquinoline 1‐oxide and related compounds
Authors: Speelman Dan , Li Jui‐Lien H. , Ramanujam V.‐M. Sadagopa , Legator Marvin S. , Albrecht Thomas
Published: February 2007

Treatment of stocks of herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) with the chemical carcinogen 4‐nitroquinoline 1‐oxide (NQO) resulted in inactivation of virus infectivity at rates which were directly dependent on the concentration of NQO and interval of exposure to NQO. HSV‐1 strains were more sensitive than HSV‐2 strains to inactivation by NQO, although survival curves of both HSV types were multicomponent. Exposure of HSV‐2 to a related group of chemicals suggested that the structural specificity required for inactivation of this virus was similar to that established by previous in vivo carcinogenicity tests.
Effects of acute and chronic administration of mitomycin C on the induction of sister chromatid exchanges in vivo
Authors: Kram David , Bynum Gaither D. , Dean Roger , Schneider Edward L. , Farland William H. , Williams Jerry R.
Published: February 2007

Frequencies of sister chromatid exchanges (SCE) were analyzed in bone marrow cells of mice injected with mitomycin C (MMC) both before and during infusion with bromodeoxyuridine (BrdU). Administration of MMC at 1, 6.5, and 13 hours after the onset of BrdU infusion resulted in the induction of approximately 45 SCE/cell, independent of time of administration. When MMC was injected 26 hours prior to BrdU infusion, only baseline levels of SCE were noted. The effects of multiple doses of MMC (chronic administration) were examined in mice treated with 1–5 mg/kg on a weekly or bimonthly basis. SCE analysis was performed one week after the final injection. At all doses and with all treatment regimes, SCE frequencies did not differ from control levels. The results indicate that most or all MMC‐induced DNA damage that results in SCE formation is removed in a single cell cycle after its administration.
Induction by inorganic metal salts of sister chromatid exchanges and chromosome aberrations in human and syrian hamster cell strains
Authors: Larramendy Marcelo L. , Popescu Nicholas C. , Dipaolo Joseph A.
Published: February 2007

Sister chromatid exchange (SCE) and chromosome aberration induction were determined for several inorganic metal salts. Arsenic, nickel, and beryllium salts at concentrations effective in causing transformation of Syrian hamster cells (HEC) induced SCE and chromosome aberrations of HEC and human lymphocytes, whereas sodium tungstate, a non‐transforming chemical, neither induced SCE nor chromosome aberrations. Normal human and hamster cells exhibited equal sensitivity to SCE induction; nontoxic concentrations of sodium arsenite, beryllium sulfate, and nickel sulfate caused an increase of 8–10 SCE/cell over control values. Sodium arsenite, a trivalent arsenic, and sodium arsenate, a pentavalent arsenic, produced increases in SCE but the former was effective at lower concentrations. Both arsenic salts were less efficient in inducing SCE in human whole blood than in purified lymphocyte cultures. Sodium arsenite, sodium arsenate, nickel sulfate, and beryllium sulfate also caused damage consisting primarily of chromatid type of aberrations. In HEC, with doses most effective in SCE induction, all four metals produced aberrations in 16–21% of cells. In human lymphocytes, 34 and 30% of the cells had chromosome damage after sodium arsenite and sodium arsenate, respectively, whereas beryllium sulfate or nickel sulfate caused damage in about 10% of the cells. The induction of SCE and chromosomal aberrations by metals reemphasizes the sensitivity of cytological assays and their importance for detecting genetic damage caused by carcinogens.
A microsuspension adaptation of the bacillus subtilis “rec” assay
Authors: McCarroll N. E. , Keech B. H. , Piper C. E.
Published: February 2007

We have demonstrated the utility of an Escherichia coli microsuspension assay to detect and characterize chemical mediation of DNA damage by a wide variety of mutagens and carcinogens. The assay has been improved by the development of a microsuspension modification to the Bacillus subtilis “rec” assay. The addition of these gram‐positive organisms has allowed detection of DNA damage induced by benzo[a]pyrene (B[a]P), 3‐aminopyrene (3‐AP), 7, 12‐dimethylbenz[a]anthracene (DMBA), 3‐methylcholanthrene (3‐MC), and 4‐nitrobiphenyl (4‐NBP). Data presented in this paper from tests of 61 additional compounds, including a representative number of direct and promutagenic agents, indicate that the B subtilis H17 and M45 strains provide an effective microbial system for identification of DNA damage susceptible to postreplicational repair. The results of this study further suggests that the inclusion of these strains in the microsuspension assay for DNA damage will markedly enhance the detection of agents which cannot readily penetrate the intact cell wall of E coli.
Mutagenicity of airborne particles from a nonindustrial town
Authors: Whong Wen‐Zong , Stewart John , McCawley Michael , Major Pervis , Merchant James A. , Ong Tong‐Man
Published: February 2007

The mutagenic activity of ambient air particles from Morgantown, West Virginia, has been monitored for 6 months using the Ames Salmonella assay system. Airborne particles, collected on glass fiber filters using a Hi‐Vol sampler, were extracted with dichloromethane (DCM) and/or ethyl acetate plus methanol (E + M) in sequence. A dose‐dependent mutagenic response was observed in Salmonella typhimurium TA 98 for DCM extracts from all samples. E + M extracts were mutagenic only when samples were extracted with E + M before DCM extraction. The mutagenic activity of samples collected in June and July was independent of S‐9 in vitro activation, whereas the mutagenicity of those collected from October to December increased in the presence of S‐9 activation. The class fractionation of extracts showed that only acidic and polynuclear aromatic fractions were mutagenic. The mutagenicity of particles from Morgantown air was also detected with the Salmonella arabinose‐resistant assay system.
Synthesis, chemical characterization, and mutagenic activities of promutagens produced by pyrolysis of proteinaceous substances
Authors: Peters John H. , Mortelmans Kristien E. , Reist Elmer J. , Sigman Caroline C. , Spanggord Ronald J. , Thomas David W.
Published: February 2007

Chemical and mutagenic characteristics of TRP‐P‐1, TRP‐P‐2, GLU‐P‐1, GLU‐P‐2, GLOB‐P‐1, and GLOB‐P‐2 were evaluated. We synthesized TRP‐P‐1 and TRP‐P‐2 and also obtained samples of these compounds from a commercial source. By GC‐MS analysis, the samples of TRP‐P‐2, GLUs, and GLOBs were more than 99% pure; but the samples of TRP‐P‐1 contained 11–17% of different impurities. These impurities had no effect on the mutagenicity of these chemicals in the Ames test using either strain TA98 or TA100 of Salmonella typhimurium. All six compounds were inactive without metabolic activation and the γ‐carbolines (TRPs) were more active in both strains than the α‐carbolines (GLOBs). GLU‐P‐1 was the most active of the promutagens tested in both TA98 (41,000 revertants/μg) and TA100 (6,580 revertants (μg). In TA98 the order of activity was GLU‐P‐1 > TRP‐P‐2 > TRP‐P‐1 > GLU‐P‐2 ≅ GLOB‐P‐2 > GLOB‐P‐1. In TA100 the order of activity was GLU‐P‐1 ≫ GLU‐P‐2 > TRP‐P‐2 ≅ TRP‐P‐1 ≫ GLOB‐P‐1 ≅ GLOB‐P‐2. We determined the UV absorption and fluorescence characteristics of these compounds, and of HM and NHM, and established an HPLC procedure for their resolution. Sensitivities in the picogram range were attainable using fluorescence detection.
Induction of sister chromatid exchanges and bacterial revertants by organic extracts of airborne particles
Authors: Lockard J. M. , Viau C. J. , Lee‐Stephens C. , Caldwell J. C. , Wojciechowski J. P. , Enoch H. G. , Sabharwal P. S.
Published: February 2007

The genotoxicities of organic extracts of airborne particles have been studied extensively in the Salmonella/mammalian microsome (Ames) test, but in few other bioassays. In these studies, we tested benzene‐acetone extracts of particulate pollutants collected in Lexington, Kentucky, for capacity to induce increases in sister chromatid exchanges (SCE) in human lymphocytes and V79 cells, as well as in the Ames assay. Extracts induced linear dose‐related increases in SCE in human lymphocytes and in bacterial revertants. However, variable responses were observed in SCE assays in V79 cells with and without activation by rat liver S9 or feeder layers of irradiated Syrian hamster fetal cells. We conclude that the SCE assay in human lymphocytes may be a useful indicator of the potential risks to humans of airborne particulate pollutants, as it utilizes human cells recently taken from the host, is rapid and economical, and requires small quantities of test materials. However, thorough studies of the quantitative relationships between SCE induction and mutagenicity in human cells are needed.
Cytotoxicity and mutagenicity of dimethylnitrosamine in mammalian cells (CHO/HGPRT system): Enhancement by calcium phosphate
Authors: O'Neill J. Patrick , Machanoff Richard , San Sebastian Juan R. , Hsie Abraham W.
Published: February 2007

The cytotoxicity and mutagenicity of dimethylnitrosamine (DMN) was determined in the CHO/HGPRT system. Metabolic activation of the promutagen was achieved by use of a liver homogenate supernatant (S9) prepared from Aroclor 1254‐induced Sprague‐Dawley rats. The cytotoxic and mutagenic effects of DMN were enhanced by the inclusion of calcium chloride in the incubation mix, and this enhancement was dependent on the presence of sodium phosphate. Under conditions that yielded maximal activity (10 mM calcium chloride, 10 mM magnesium chloride, 50 mM sodium phosphate), an apparent calcium phospate precipitate was observed. DMN activity increased with increasing amounts of S9 protein over the range 0.3–3.0 mg/ml in the S9 mix and appeared to plateau at higher concentrations. The mutagenicity of DMN can be described as 110 mutants/106 cells per mM DMN per mg/ml S9 protein per hour.
Comparison of the genotoxic activities of extracts from ambient and forest fire polluted air
Authors: Viau C. J. , Lockard J. M. , Enoch H. G. , Sabharwal P. S.
Published: February 2007

The genotoxicity of airborne organic particles from forest fire smoke was compared to that from nonsmoky (ambient) urban air using the Salmonella reversion assay and the sister chromatid exchange (SCE) assay in cultured human lymphocytes. Salmonella strains TA98 and TA100 were used with and without the addition of Aroclor‐induced rat liver homogenate (S9). Each sample induced dose‐related increases in mutagenicity and SCE. However, on the basis of the volume of air sampled, the smoke‐filled air induced 12 to 14 times more bacterial reversions in TA100 and 16–38 times more reversions in TA98 than ambient air. Similarly, on a volume basis smoky air induced 43 times more SCE in human lymphocytes than did ambient air. The results indicate that the increased mutagenicity was due not only to the heavier particulate load of the air, but also to the increased specific mutagenicity of the particles.