bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the in vivo aneuploidy/micronucleus assay in mouse bone marrow cells with 16 chemicals
Authors: Gudi Ramadevi , Xu Jing , Thilagar Arul 
Published: February 2007

AbstractAssessment of the in vivo aneuploidy/micronucleus Assay in bone marrow cells with 16 chemicals is described. This assay is based on the detection of kinetochores (KC) in micronuclei (MN) by antikinetochore‐specific (CREST) antibodies. Among sixteen chemicals tested, six were known clastogens, three were known aneuploidy‐inducers, and the other seven were suspected spindle poisons. These chemicals were tested for their ability to induce micronuclei with kinetochore(s) in bone marrow cells of CD‐1 mice. The majority of MN formed in bone marrow cells treated with aneuploidy‐inducing agents contained kinetochore(s) which are considered to be formed from whole chromosomes or centric fragments, while in clastogen treated bone marrow cells, majority of them contained no kinetochore(s) which are considered to be formed from acentric chromosomal fragments. Classification of chemicals into either aneuploidy inducing agents or clastogens is based on the relative frequency of MN with and without KC, respectively. These results suggest that the in vivo aneuploidy/micronucleus assay has a great potential to identify aneuploidy‐inducing agents. © 1992 Wiley‐Liss, Inc.
Cytogenetic effects of vincristine sulfate and ethylene dibromide in human peripheral lymphocytes:Micronucleus Analysis
Authors: Channarayappa  , Ong T. , Nath J. 
Published: February 2007

AbstractMicroncuclei kinetics and persistence in mononucleated and binucleated human peripheral lymphocytes following short‐term (4 hr) and continuous (until harvest) in vitro exposure to vincristine sulfate (VS) and ethlylene dibrode (EDB) were studied. Lymphocytes were exposed to chemicals for various doses and harvested at different culture times. Micronucleus frequenvies were scored in both mononucleated and biucleated cells on the same slide. VS‐treated cells showed a significantly higher incidence of micronucleus in both ononucleated and binucleated cells than controls (p<0.01). The cells treated continuously with VS produced comparatively higher frequencies of micronucleated cells than those treated for 4 hr. Highest micronuclei frequencies were observed 24 hr after chemical treatment in both mononucleated and binucleated cells and decreased later with time. However, the micronucleus frequencies remained significantly higher than the controls even in the cells harvested at 144 hr. VS induced a large number of micronucleated cells with multiple micronuclei. VS also caused a severe decrease in nuclear division due to cytotoxic effect. Lymphoctes treated with EDB for 4 hr and continuously showed a statistically higher incidence of micronuclei in binucleated cells compared to the controls (p<0.05), whereas in mononucleated cells higher micronucleus frequencies were observed only in cultures treated continuously. Continuous presence of EDB induced both dose‐and time‐dependent increase of micronuclei in both mono‐ and binucleated cells(p<0.05). EDB induced relatively few multiple micronucleated cells in comparison with VS. EDB did not affect nuclear divisions even with continuous treatment. HIgh micronucleus frequencies observed at 144 hr harvest following 4 hr treatment of both EDB and VS suggest the persistence of DNA damage in cells. These studies suggest that micronuclei kinetics in human periphearl lymphocytes depends on the genotoxic potentially and cytotoxicity of a geno toxicant. © 1992 Wiley‐Liss, Inc.
Mechanisms for dominance: Adh Heterodimer formation in heterozygotes between ENU or X‐ray induced null alleles and normal alleles in Drosophila melanogaster
Authors: Jiang James C. , Lee William R. , Chang S. H. , Silverman Harold 
Published: February 2007

AbstractMechanisms for Dominance: Adh Heterodimer Formation in Heterozygotes Between ENU or X‐ray Induced Null Alleles and Normal Alleles in Drosophila melanogasterTo study mechanisms for dominance of phenotype, eight ENU‐ and four X‐ray‐induced mutations at the alcohol dehydrogenase (Adh) locus were analyzed for partial dominance in their interaction with normal alleles. All ENU and one of the X‐ray mutations were single base substitutions; the other three X‐ray mutations were 9–21 base deletions. All but one of the 12 mutant alleles were selected for this study because they produced detectable mutant polypeptides, but seven of the 11 producing a peptide could not form dimers with the normal peptide and the enzyme activity of heterozygotes was about half that of normal homozygotes. Four mutations formed dimers with a decreased catalytic efficiency and two of these were near the limit of detectability; these two also inhibited the formation of normal homodimers. The mutant alleles therefore show multiple mechanisms leading to partial enzyme expression in heterozygotes and a wide range of dominance ranging from almost complete recessive to nearly dominant. All amino acid changes in mutant peptides that form dimers are located between amino acids 182 and 194, so this region is not critical for dimerization. It may, however, be an important surface domain for catalyzation. © 1992 Wiley‐Liss, Inc.
Investigation of the mutagenic specificity of x‐rays using a retroviral shuttle vector in cho cells
Authors: Skandalis A. , Grosovsky A. J. , Drobetsky E. A. , Glickman B. W. 
Published: February 2007

AbstractIn some biological systems ionizing radiation appears to induce large deletions and rearrangements, while in others point mutations predominate the mutational spectrum. Moreover, while the point mutations are often randomly distributed, some systems exhibit “hot spots.” Retroviral shuttle vectors are particularly useful for investigating the basis of these differences since the genetic target can be conveniently analyzed in a variety of host backgrounds and genomic locations. We have studied the mutational specificity of X‐rays in a Chinese hamster ovary cell line (CHO) containing a stably integrated retroviral shuttle vector, carrying the CHO aprt cDNA as the genetic target. Cells were irradiated with 7 Gy using a 180 kVp X‐ray source. The predominant mutation (87% of all APRT mutants), as determined by Southern analysis, was the complete deletion of the shuttle vector construct. In addition, 23 APRT mutants, carrying an apparently intact shuttle vector, were characterized at the sequence level: 5 were transitions, 9 were transversions, 3 were small deletions or insertions, 4 were frameshifts, and 2 were small rearrangements. Although the type and the location of the point mutations character ized appeared largely random, small deletions, insertions, and frameshifts were frequently associated with direct sequence repeats. © 1992 Wiley‐Liss, Inc.
DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or heat tobacco
Authors: Lee C. K. , Brown B. C. , Reed E. A. , Hejtmancik M. , Mosberg A. T. , Doolittle D. J. , Hayes A. W. 
Published: February 2007

AbstractA prototype cigarette that heats tobacco (test cigarette), developed by R.J. Reynolds Tobacco Company, has yielded consistently negative results in several in vivo and in vitro genetic toxicology tests. The objective of the present study was to evaluate the potential of cigarette smoke condensate (CSC) from the test cigarette to induce DNA adducts in mouse tissues and compare the results with those obtained with CSC from a reference tobacco‐burning cigarette (1R4F). CD‐I mice were skin‐painted with CSC from reference and test cigarettes three times a week for 4 weeks. The highest mass of CSC applied was 180 mg “tar” per week per animal for both reference and test cigarette. DNA adducts were analyzed in skin and lung tissues using the 32P‐postlabeling method with the P1, nuclease modification. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from both skin and lung tissues of animals dosed with reference CSC, whereas no corresponding DRZ were observed from the DNA of animals closed with either test CSC or acetone (solvent control). The relative adduct labeling (RAL) values of skin and lung DNA from reference CSC‐treated animals were significantly greater than those of the test CSC‐treated animals. The RAL values of the test CSC‐treated animals were no greater than those of solvent controls. The negative results in DNA adduct assays with test CSC are consistent with all previous results of in vivo and in vitro genetic toxicology testing on this cigarette and provide additional evidence that smoke condensate from the test cigarette is not genotoxic. © 1992 Wiley‐Liss, Inc.
Structural basis of the mutagenicity of heterocyclic amines formed during the cooking processes
Authors: Zhang Ying Ping , Klopman Gilles , Rosenkranz Herbert S. 
Published: February 2007

AbstractA data base consisting of 61 heterocyclic amines formed during food preparation and their desamino analogs were subjected to structure‐activity analysis using the CASE method, a structural activity relational expert system. The program identified the major structural determinants associated with mutagenic activity or lack thereof. The structures identified as contributing to the probability of activity as well as those associated with mutagenic potency were highly predictive of molecules not in the learning set. The major structural determinant, the aromatic amino moiety, and quantum mechanical calculations revealed that the mutagenic potency associated with this functionality derived from their contribution to the energy of the Lowest Unoccupied Molecular Orbital (LUMO.) © 1993 Wiley‐Liss, Inc.
Insertional mutagenesis by transposable elements in the mammalian genome
Authors: Amariglio N. , Rechavi G. 
Published: February 2007

AbstractSeveral mammalian repetitive transposable genetic elements were characterized in recent years, and their role in mutagenesis is delineated in this review. Two main groups have been described: elements with symmetrical termini such as the murine IAP sequences and the human THE 1 elements and elements characterized by a poly‐A rich tail at the 3′ end such as the SINE and LINE sequences. The characteristic property of such mobile elements to spread and integrate in the host genome leads to insertional mutagenesis. Both germline and somatic mutations have been documented resulting from the insertion of the various types of mammalian repetitive transposable genetic elements. As foreseen by Barbara McClintock, such genetic events can cause either the activation or the inactivation of specific genes, resulting in their identification via an altered phenotype. Several disease states, such as hemophilia and cancer, are the result of this apparent aspect of genome instability. © 1993 Wiley‐Liss, Inc.
Formation and characterization of bacterial mutagens from reaction of the alternative disinfectant monochloramine with model aqueous solutions of fulvic acid
Authors: Cozzie D. A. , Kanniganti R. , Charles M. J. , Johnson J. D. , Ball L. M. 
Published: February 2007

AbstractMonochloramine has been suggested as an alternative disinfectant to chlorine to reduce levels of trihalomethanes in treated drinking water, but little is known of the toxicological properties and potential health implications of by‐products specific to the chloramination process. Model aqueous fulvic acid solutions (200–400 mg C/liter), serving as surrogates for humic surface waters, were chloraminated over a range of molar Cl:C ratios from 1:40 to 1:2. The resulting by‐products were extracted into diethyl ether at pH 2 and investigated with the Ames plate incorporation assay. Extractable mutagenicity increased with increasing chlorine and carbon dose up to about 30,000 revertants/liter at Cl:C ratios of 1:2. Mutagenicity was higher in Salmonella typhimurium strain TA100 than in strain TA98, and was decreased in the presence of S9, indicating that the mutagens formed were direct‐acting and induced predominantly base‐pair substitutions. Bovine serum albumin decreased slightly, and glutathione reduced greatly, the mutagenic activity detected in extracts. HPLC fractionation of the by‐products indicated that most of the mutagenic activity was found in the earliest‐eluting (most polar) fraction. The mutagenic by‐products appeared to be qualitatively similar to 3‐chloro‐4‐dichlorome‐thyl‐5‐hydroxy‐2‐(5H)‐furanone (MX) in their chromatographic behavior and responses to glutathione and bovine serum albumin, but were less readily detoxified by S9 than was MX. © 1993 Wiley‐Liss, Inc.
Mutagenicity of iso‐butyl nitrite vapor in the ames test and some relevant chemical properties, including the reaction of iso‐butyl nitrite with phosphate
Authors: Mirvish Sidney S. , Williamson Jan , Babcook David , Chen Sheng‐Chong 
Published: February 2007

AbstractWe examined the mutagenicity of iso‐butyl nitrite (IBM) vapor and aqueous IBN solution in the Ames test to help evaluate the hazard of sniffing this vapor, a habit which might play a role in the induction of Kaposi's sarcoma associated with acquired immune deficiency syndrome. Chemical analysis showed that the saturated vapor contained 190 μg IBM/ml at 25°C, and saturated aqueous solution, 2.6 mg IBN/ml at 2J‐23°C When agar plates containing Salmonella typhimurium TA‐1535 and rat liver S‐9 were exposed to IBN vapor, the number of mutants reached a maximum after 40 min. A mean of 307 mutants/plate (22 × background) was observed when the plates were exposed to IBN vapor for 30 min. Addition of 0.2 ml saturated IBN solution in water to similar plates gave a mean of 179 mutants/plate (7.9 × background) in the absence of S‐9, confirming published results. The S‐9 did not affect the results. Based on the IBN level in medium exposed to IBN vapor, the vapor was apparently 11 times more mutagenic than IBN solution. This was attributed to continuous replenishment of unstable IBN in the medium by the vapor. The half‐life of IBN at 21–23°C was >1 hr for solutions in water and <3 min for solutions in the assay medium. This instability was traced to a reaction with phosphate, presumably hydrolysis to nitrite and iso‐butanol. IBN in solution was 2.8 times more mutagenic than sodium nitrite, suggesting that IBN was not mutagenic because of its conversion to nitrite, Iso‐butanol was not mutagenic. The results demonstrate the potential hazard of sniffing IBN vapor. © 1993 Wiley‐Liss, Inc.
Evaluation of the potential of riddelliine to induce unscheduled DNA synthesis, S‐phase synthesis, or micronuclei following in vivo treatment with multiple doses
Authors: Mirsalis Jon C. , Steinmetz Karen L. , Blazak William F. , Spalding Judson W. 
Published: February 2007

AbstractRiddelliine (RID) is a pyrrolizidine alkaloid found in plants of the genera Crotalaria, Amsinckia, and Senecio in the United States. RID has been extensively studied in a wide variety of in vitro short‐term genotoxicity tests and has yielded positive responses in most test systems; however, there are fewer data available on the effects of RID in in vivo assays and no data under repeat‐dose regimens. We have evaluated the ability of RID to induce unscheduled DNA synthesis (UDS) in hepatocytes, S‐phase synthesis (SPS) in hepatocytes, and micronuclel in bone marrow from animals dosed for 5 or 30 days in conjunction with prechronic toxicity testing conducted for the National Toxicology Program. Results of this study indicate that RID did not induce an increase in micronucleated polychromatic erythrocytes (PCE) in bone marrow of mice after 5 days of dosing or in PCE from rats or mice after 30 days of dosing. RID did not induce an increase in UDS in rat hepatocytes after 5 or 30 days of dosing, but it did induce an equivocal UDS response in male mice after both time points and a positive response in female mice after 30 days of dosing. RID induced significant elevations in SPS in rat hepatocytes after both 5 and 30 days of dosing, even at low doses. An increase in SPS was observed in male and female mouse hepatocytes, but only after 30 days of dosing. Rats and mice of both sexes showed a depression in SPS at higher doses. This effect may be a result of toxicity, which compromises the ability of the liver to regenerate. These results demonstrate that repeated administration of test chemicals may alter the genotoxic response to chemicals. © 1993 Wiley‐Liss, Inc.
Analysis of restriction enzyme‐induced chromosomal aberrations by fluorescence in situ hybridization
Authors: Columna Elma Abella , Giaccia Amato J. , Evans James W. , Yates Barbara L. , Morgan William F. 
Published: February 2007

AbstractFluorescence in situ hybridization and Giemsa staining of metaphase chromosomes were used to determine the relative frequencies of symmetric exchange aberrations (translocations) and asymmetric exchange aberrations (rings, dicentrics, and polycentrics) after exposure of human lymphoblastoid cells to restriction enzymes or X‐rays. The yield of symmetric exchanges was determined with the use of chromosome‐specific probes for human chromosomes 2 or 4, which were hybridized to metaphase chromosomes from cells exposed to the enzymes Pvull, Sacl, or Xbal or 3 or 5 Gy of X‐rays. The yield of asymmetric exchanges was determined in Giemsastained metaphase chromosomes from the same enzyme‐treated or irradiated cell population. About 1.5‐ to 3‐fold more symmetric than asymmetric exchanges were induced after restriction enzyme treatment. However, after X‐ray treatment the yield of dicentrics relative to the yield of reciprocal translocations was close to the expected 1:1 ratio.
Effect of temperature on frequencies of spots in drosophila wing‐spot assay
Authors: Katz Alan J. , Foley Teresa A. 
Published: February 2007

AbstractThe effect of temperature on spontaneous mutation frequencies was studied in the Drosophila somatic mutation and recombination test. Transdihybrid mwh +/+ flr3 larvae were grown at various temperatures (15, 18, 20, 22, 25, 27, and 29°C) in the absence of any chemical mutagen. Wings of surviving adults were removed and scored for presence of small single spots, large single spots, and twin spots. No significant effect of temperature was found on mean frequency per wing of twin spots. Similarly, no significant effect of temperature was found for large singles within the temperature range of 18–29°C; however, at 15èC, the mean frequency per wing of large spots was significantly elevated. A significant quadratic relationship was found between mean frequency of small spots and temperature. Frequency of small spots per wing was minimized within the temperature range of 20‐27°C and increased at higher and lower temperatures. Maximum frequency of small spots per wing was observed at 15°C. The qualitative nature of the small single spots induced at high and low temperatures is unclear; they may represent slow‐growing segmentally aneuploid (deleted) cells or possibly even monosomic cells. Both heat and cold were found to be mutagenic in the Drosophila wing‐spot assay. However, the mutagenic potency associated with temperature was much less than that of most chemical mutagens, and no significant effect of temperature was observed in the range of 20–27°C. © 1993 Wiley‐Liss, Inc.
Molecular analysis of hypoxanthine phosphoribosyl transferase mutants induced by glycidyl 1‐naphthyl ether in mouse spleen cells in vivo
Authors: Tan R. S. , Chu E. H. Y. , Sinsheimer J. E. 
Published: February 2007

AbstractTreatment of C57BL/6J mice with an epoxide, glycidyl 1‐naphthyl ether (GNE), resulted in an average of a 3.4‐fold increase in frequency of 6‐thioguanine‐resistant mutants of mouse spleen T‐lymphocytes. In similar experiments with the epoxide trichloropropylene oxide, no increase in mutant frequency was found. To determine the kind and location of mutations in the coding region of the hypoxanthine phosphoribosyl transferase (HPRT) gene, 26 GNE‐induced mutants and 17 spontaneous mutants were analyzed by direct sequencing of polymerase chain reaction amplified cDNA. Among the GNE‐induced mutants, HPRT cDNA was present in 22, while that from 4 could not be detected. Among the spontaneous mutants, HPRT cDNA was present in 15 and absent in 2. Among GNE‐induced mutants, base substitution in HPRT occurred in 15 of 22 mutants analyzed. Nine of 15 base substitutions involved TA base pairs, primarily TA→CG transitions. Base substitutions were found throughout exons 3–7 but 46% of substitutions were located in exon 3 and one frameshift mutation involving a GC base pair in exon 3 was also observed. Among the spontaneous mutants, base substitutions of HPRT occurred in 7 of 15 mutants analyzed with 6 of 7 base substitutions involving a TA base pair and another 2 of the 15 mutants showed a 4 base pair deletion. The base substitution spectrum in GNE‐induced mutants was different from that of the spontaneous mutants. © 1993 Wiley‐Liss, Inc.
Amesfit: A microcomputer program for fitting linear‐exponential dose‐response models in the ames salmonella assay
Authors: Leroux Brian G. , Krewski Daniel 
Published: February 2007

AbstractThe Ames Salmonella/microsome assay remains the most widely used microbial test for genotoxicity. In this article, we describe a microcomputer program developed to fit a linear‐exponential dose‐response model to Ames assay data for established mutagens. The model includes a linear term to describe the mutagenic effects of the test agent at low to moderate doses and an exponential attenuation factor to accommodate downturns at high doses due to cytotoxicity. Quasi‐likelihood methods are used to obtain estimates of the unknown model parameters, thereby avoiding the need to fully specify the distribution of the experimental data. This method of estimation also allows for extra‐Poisson variation that is characteristic of counts of mutant colonies of bacteria observed in the Ames assay. The particular linear‐exponential model used here was developed for use in the analysis of a recent large‐scale collaborative trial using the Ames assay sponsored by the International Programme on Chemical Safety. The use of our program is illustrated using sample data sets taken from that collaborative study. © 1993 Wiley‐Liss, Inc.
Investigation of aneuploidy induction in mouse oocytes following exposure to vinblastine‐sulfate, pyrimethamine, diethylstilbestrol diphosphate, or chloral hydrate
Authors: Mailhes John B. , Aardema Marilyn J. , Marchetti Francesco 
Published: February 2007

AbstractThe various causative and mechanistic phenomena associated with aneuploidy induction require considerable investigation to better understand the etiology of chromosome missegregation. We investigated the potential of vinblastine sulfate, pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate to induce numerical and structural chromosome changes in female mouse germ cells. Superovulated ICR mice were administered the compounds either by intraperitoneal injection or oral gavage, and oocytes were collected and processed for cytogenetic analysis 17 hr later. Vinblastine sulfate, administered i.p., induced a significant increase in the frequency of ovulated Ml oocytes and of hyperploid Mll oocytes compared to controls, but did not increase the frequency of structural aberrations. Pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate did not increase the frequency of numerical or structural chromosome changes in female mouse germ cells. © 1993 Wiley‐Liss, Inc.