bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose‐dependent genotoxic effects of styrene on human blood lymphocytes and the relationship to its oxidative and metabolic effects
Authors: Chakraborti Saroj , Duhr Marie‐Ange , Senécal‐Quevillon Micheline , Richer Claude‐Lise 
Published: February 2007

AbstractAlthough the genotoxic potential of styrene is known, very limited information is available regarding its dose‐dependent genotoxic response to human blood lymphocytes and how such response correlates with different metabolic events in whole blood lymphocytes. The present study was therefore carried out to study such a relationship using in vitro human blood lymphocytes from healthy volunteers. To study genotoxic response to styrene, sister chromatid exchanges (SCEs), cell cycle, and cell survival were analyzed. Lymphocytes were cultured for 72 hr in the presence of different concentrations of styrene (0–1,000 μM). Twenty‐four hr before harvest, BrdU (5 μg/ml) was added to assess the increase in SCEs and cell cycle delay. Both the SCE frequency and the cell cycle length were increased linearly with increasing concentrations of styrene up to 200 μM, without addition of any exogenous metabolizing system. Above 200 μM, no further increase in genotoxic response occured. The range of concentrations (10–200 μM) at which increase of cell cycle length due to styrene was observed did not impair the viability of the cells, suggesting that such cell cycle delay is a genotoxic‐related event and not caused by cytotoxicity. In vitro metabolic transformation of styrene in whole‐blood lymphocyte cultures without the presence of any exogenous metabolic activation system showed the formation of a reactive intermediate, styrene 7,8‐oxide, to be capacity‐limited, as verified from a nonlinear increase in the formation of styrene glycol. The value of such metabolic parameter reached a plateau above 200 μM styrene. The same phenomenon of saturation has also been observed with regard to other metabolic effects due to styrene in whole blood lymphocytes in culture, such as dose‐dependent increase in lipid peroxidation and depletion of blood lymphocyte glutathione. Based on the relationship between the formation of different metabolic events and the genotoxicity of styrene, it may be possible that the genotoxic properties of styrene in human blood lymphocytes may be mediated initially not only by the formation of the presumably reactive styrene 7,8‐oxide, but also by that of a reactive oxygen species as well. However, the present data are not sufficient enough to definitely identify the role of reactive oxygen species in such toxicity and therefore it warrants further study. © 1993 Wiley‐Liss, Inc.
p53 mutations in human bladder cancer
Authors: Kusser Wolfgang C. , Miao Xili , Glickman Barry W. , Friedland Joan M. , Rothman Nathaniel , Hemstreet George P. , Mellot John , Swan David C. , Schulte Paul A. , Hayes Richard B. 
Published: February 2007

AbstractMutations in the tumor suppressor gene p53 play an important role in carcinogensis and tumor progression. To assess the status of p53 from genomic DNA from bladder cancer samples a two stage polymerase chain reaction was employed. The technique provided material for subsequent detection of mutations by Single Strand Conformation Polymorphism (SSCP) analysis followed by DNA sequence analysis. SSCP analysis of exons 5 to 9 of p53 was performed using fragments from PCR end‐labeled with 32P followed by autoradiography using an electrophoresis system with temperature control. This SSCP method improved resolution of mutations in exons 5, 7, and 8 and the sharpness of bands in exons 6 and 9. Bands with altered migration patterns were excised from the dried SSCP gels, reamplified by PCR, and sequenced. Mutations in conserved exons 5, 6, 7, 8, and 9 of the p53 gene were analyzed from bladder tumor biopsies. Our results are consistent with the literature in that mutations in p53 are predominantly found in high grade bladder cancer (Odds Ratio = 4.05, Fisher Exact P = 0.104); however, the results were not statistically significant due to small numbers. Eight of 35 (23%) tumor samples examined showed mutations in p53 (including two double mutations). Six of 13 (46%) grade III and IV tumors had p53 mutations vs. 2 of 17 (12%) grade I and II tumors. Normal individuals carried no p53 mutations. We found no correlation between pack years of smoking and mutation in p53. The spectrum of mutations confirmed a high proportion of G:C C:G transversions as well as the occurrence of double mutations. © 1994 Wiley‐Liss, Inc.
Statistical tests of significance in transgenic mutation assays: Considerations on the experimental unit
Authors: Carr G. J. , Gorelick N. J. 
Published: February 2007

AbstractWhen significant animal‐to‐animal variability is present in binary response data, the usual statistical tests applied to such data do not always operate correctly. In transgenic mouse mutation data, some evidence of significant animal‐to‐animal variability already exists, suggesting that conventional statistical methods may not be appropriate. Here, we describe an alternative statistical method that treats the animal as the experimental (or statistically independent) unit, and contrast results of its application with those from methods that take the transgene as the experimental unit. Using data from two publications that report experimental results for individual animals, the transgene‐based and animal‐based analyses can yield very different interpretations of the experimental data. The performance of animal‐based statistical methods should be improved by conducting future experiments with enough animals to adequately address animal‐to‐animal variability. © 1994 Wiley‐Liss, Inc.
Hprt mutant frequency and GSTM1 genotype in non‐smoking healthy individuals
Authors: Hou Sai‐Mei , Fält Susann , Steen Ann‐Marie 
Published: February 2007

AbstractThe T‐cell cloning assay which combines mito‐gen‐ and growth factor‐dependent expansion of lymphocyte clones with thioguanine selection of hypoxanthine‐guanine phosphoribosyl trans‐ferase (hprt)‐negative cells has been extensively used for studying human somatic gene mutation in vivo. However, large interindividual variations in the hprt mutant frequency (MF), much of which is not explained by donor attributes such as age and smoking habit, and interlaboratory variations in the experimental methodology, including cloning efficiency (CE), call for further developments of the cloning protocol and additional population studies. Using an improved T‐cell cloning method, we have studied in vivo hprt MF of 76 non‐smoking healthy males aged 23–77 years. The addition of 5% human serum to the growth medium was found to produce a consistently high CE of 61% in average. The MF, ranging from 1.4 to 22.6 × 10−6 with a mean of 8.6 × 10−6, increased significantly (P < 0.0001) with age, by 2% per year. A significant (P = 0.002) inverse relationship between MF and CE was observed. Using a PCR‐based technique for GSTM1‐genotyping, we also studied the relationship between MF and GSTM1 polymorphism. The 38 (50%) GSTM1‐negative individuals showed a 20% higher mean MF than the 38 (50%) GSTM1‐positive individuals. The difference was however not significant, neither before (P = 0.1) nor after (P = 0.5) correction for CE and the significantly (P = 0.04) higher mean age in the GSTM1‐negative group. This study shows that age contributes more than GSTM1 polymorphism to the large interindividual variation in the hprt MF of non‐smokers. The relationship between GSTM1 polymorphism and hprt MF in smokers remains to be investigated. © 1995 Wiley‐Liss, Inc.
Effects of vinblastine and colchicine on male rat meiosis in vivo: Disturbances in spindle dynamics causing micronuclei and metaphase arrest
Authors: Kallio Marko , Sjöblom Tiina , Lähdetie Jaana 
Published: February 2007

AbstractWe have studied the effects of vinblastine sulfate (VBL) and colchicine (COL) on male rat in vivo and in vitro meiosis. A novel methodology based on isolating a segment of seminiferous tubules containing meiotically dividing spermatocytes was applied. During meiotic divisions at stage XIV of rat spermatogenesis, both chemicals induced only low frequencies of micronu‐clei (MN), 0.8–3.2 MN/1,000 spermatids. Fluorescence in situ hybridization experiments in mice with the mouse centromere‐specific y‐sat‐ellite DNA probe showed that 50.7% of VBL‐induced MN and 56.6% of COL‐induced MN were centromere positive, indicating that the MN induced by both chemicals contained detached chromosomes. The inhibition of cell proliferation was determined by counting the number of cells arrested at metaphase during the first meiotic (MI) or the second meiotic (MII) division. VBL was found to be a potent inducer of cell death while COL was not. The direct effects of VBL and COL on the meiotic spindles were evaluated using immunohistochemistry with anti‐a‐tubulin and confocal microscopy. In the control animals a significant difference was observed between the mean length of metaphase spindles of MI and MII Both were dramatically decreased 6 hr after treatment with 2.0 mg/kg of VBL and 0.8 mg/kg of COL, respectively. At 18 hr after COL injection the spindles had about the same length as in the controls. However, the VBL‐induced shortening was even more evident at 18 hr for both Ml and Mll. The possible reasons for observed differences between the two chemicals and between meiosis and mitosis are discussed. © 1995 Wiley‐Liss, Inc.
Aneugen‐induced micronuclei (MN) in human lymphocytes may be discerned using image analysis techniques when cell‐cycle stage is taken into account
Authors: Van Hummelen P. , Nüsse M. , Castelain P H. , Kirsch‐Volders M. 
Published: February 2007

AbstractWe show that for the in vitro cytochalasin‐B human lymphocyte micronucleus (MN) test, the quantification of the DNA content of MN and the difference in DNA content between the two macronuclei in the binucleate cells without MN, as measured by image analysis, gives a first estimation of the aneugenic potential of a test compound. Cultures of isolated human lymphocytes were exposed either to γ‐rays as a clastogen or to carbendazim (MBC) as an an‐eugen. The lymphocytes were stained with Feulgen stain and the MN were analyzed for DNA content with a Magiscan 2A image analyzer. The mean DNA content of MN induced by MBC were statistically higher than γ‐irradiation‐induced MN. It was demonstrated that in culture the lymphocytes, as well as the MN, are in different stages of the cell cycle, but this will not affect the discriminating power of the MN DNA content when only G1 cells are considered, or when DNA content of the MN is expressed relative to the total genome. The identification of Gl and G2 cell populations from image analysis data was performed by extrapolation of DNA content data from Gl‐ and G2‐sorted lymphocytes with a FacStar plus flow sorter. It was demonstrated that in MBC‐treated cells the DNA rearrangement between the macronuclei in binucle‐ates without MN was on the average higher than in γ‐irradiated and untreated cells, which points to aneugenic effects of MBC without the formation of MN. In contrast to DNA content measurements, the area of the MN is not a reliable measure for discriminating clastogens from aneugens. © 1995 Wiley‐Liss, Inc.
Micronuclei in mice treated with monocrotaline with and without phenobarbital pretreatment
Authors: Higgins Michael J. , Ficsor Gyula , Aaron C. S. , Petry Thomas W. , Yu Roger L. , Friedman Stephen B. 
Published: February 2007

AbstractMonocrotaline is a very potent toxin, producing significant effects of pneumotoxicity, hepatotoxicity, and teratogenicity, as well as carcinogenicity. In addition, the compound has been clearly shown to be muta‐genic after metabolic activation. The goal of the experiments reported here was to confirm the reported clastogenesis induced by this agent in vivo and to evaluate the impact of modulation of metabolic activity by phenobarbital, a potent P‐450 inducer (both Phase I and Phase II enzymes). The method used in addressing this problem relied on a new technique for monitoring clastogenesis in vivo, i.e., the acridine orange micronucleus assay method originally exploited by Hayashi et al. [1990].The result of our experiments confirmed monocro‐taline to be an effective clastogen in vivo, using the acridine orange method of assessment. The peak in induction of micronuclei occurred on the second day following intraperitoneal administration of the drug. Administration of phenobarbital prior to monocrotaline did appear to modulate the micronucleus induction. At 30 mg/kg bw monocrotaline, the pretreatment with phenobarbital appears to increase the intensity of monocrotaline clastogenesis, while the effect at higher doses (60 and 125 mg/kg bw) is a reduction in potency, presumably reflecting increased importance of Phase II metabolism for monocrotaline at these doses. Thus the study reported here confirms the potent in vivo clastogenesis of monocrotaline, and provides evidence for a dose‐related shift in mechanism for the phenomenon. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity in asbestos‐induced mutations in a human mesothelioma cell line
Authors: Both Katrin , Turner David R. , Henderson Douglas W. 
Published: February 2007

AbstractThe relationship between occupational or environmental exposure to asbestos and the development of mesothelioma, typically after prolonged latency, has been accepted as one of cause and effect. Most studies have concluded that asbestos is not mutagenic to mammalian cells in vitro. We have studied the potential of crocidolite asbestos to induce mutations in a stable mesothelioma cell line, using a mutation assay that measures mutation at the autosomal HLA‐A locus and permits clonal growth of mutant cells. The mesothelioma cell line chosen is more akin to the in vivo target cells of asbestos than human peripheral blood lymphocytes used in previous studies. Exposure of mesothelioma cells in culture to both 200 μg/ml and 50 μg/ml crocidolite for 72 hr did not result in a statistically significant difference in the mutation frequency (MF) in the HLA‐A assay when compared to the spontaneous MF in these cells. Mutations in the mesothelioma cells were classified according to their molecular basis. Notwithstanding the lack of statistically significant change in overall MF, molecular analysis of mutants obtained following exposure of mesothelioma cells to crocidolite demonstrated a statistically significant increase in the class of mutations arising from loss of heterozygosity (LOH) events involving the selection locus (HLA‐A) and more distal loci. Mutations following exposure to 200 μg/ml and 50 μg/ml crocidolite showed a greater frequency of LOH than did spontaneous mutants (P < 0.01 and P < 0.001, respectively). These results correlate with those obtained in an earlier study using lymphocytes. The mesothelioma cell‐based assay may be useful in detecting the mutagenicity of other asbestiform fibers and man‐made fibers. © 1995 Wiley‐Liss, Inc.
Relationships among in vitro mutagenicity assays: Quantitative vs. qualitative test results
Authors: Benigni Romualdo , Andreoli Cristina , Giuliani Alessandro 
Published: February 2007

AbstractIn previous investigations, we studied the relationships between the profiles of the qualitative responses of in vitro short‐term tests (mutation in Salmonella typhimurium, chromosomal aberrations in CHO cells, sister chromatid exchanges in CHO cells, and mutation in mouse lymphoma cells) and common sets of chemicals. In this paper, we address the study of the quantitative responses (potency). We show that two analyses point to similar patterns of relationships: the mutation in mouse lymphoma cells assay is most similar to the CHO sister chromatid exchange assay, and the Salmonella assay is most similar to the CHO chromosomal aberrations assay. © 1995 Wiley‐Liss, Inc.
Genotoxic effects of p‐aminophenol in chinese hamster ovary and mouse lymphoma cells: Results of a multiple endpoint test
Authors: Majeska Jenness B. , Holden Henry E. 
Published: February 2007

Abstractp‐Aminophenol (PAP), a metabolite of aniline and acetaminophen, has been reported to be mutagenic in the L5178Y mouse lymphoma assay, but not in the CHO/HGPRT assay. In the present study, the effects of PAP in these two cells lines were examined to determine if the difference in activity is related to an intrinsic difference in the cell lines. CHO and L5178Y +/− mouse lymphoma cells were treated with PAP for 4 hr and assayed for 3 genetic endpoints: gene mutation at the HGPRT or TK locus, respectively; chromosomal aberrations at approximately 20 hr after initiation of treatment; and single‐stand DNA breaks as detected by the single cell electrophoresis assay immediately after treatment. All treatments were conducted in the absence of S9. There was a dose‐related, significant increase in TFT‐resistant mouse lymphoma cells at dose levels that reduced survival to ⩽=50% of concurrent controls. In CHO cells, however, there was no increase in thioguanine‐resistant cells at dose levels that reduced cell survival to < 20%. These results are consistent with published reports on PAP. While the CHO cells were slightly more resistant to the toxic effects of PAP, the dose levels used in the two cell lines did not differ by more than 2‐fold. At equivalent survival levels, PAP induced a significant (up to 20% aberrant cells) number of aberrations, primarily complex rearrangements, in both cell lines. In the single cell electrophoresis assay, there was a reproducible dose‐related increase in cells with single‐strand DNA breaks with both the L5178Y cells and the CHO cells. The induction of single‐strand breaks and chromosome aberrations by PAP suggests that, mechanistically, PAP produces similar genetic damage in both CHO and L5178Y cell lines, but intrinsic differences between assay systems are responsible for the divergent gene mutation results. © 1995 Wiley‐liss, Inc.
Atrazine treatment potentiates excretion of mutagenic urine in 2, 6‐dinitrotoluene‐treated fischer 344 rats
Authors: George S. E. , Chadwick R. W. , Kohan M. J. , Allison J. C. , Warren S. H. , Williams R. W. 
Published: February 2007

AbstractAtrazine (ATZ), an s‐triazine herbicide, is a widespread environmental contaminant. The hepatocar‐cinogenic component of technical grade dinitrotoluene, 2, 6‐dinitrotoluene (2, 6‐DNT, 19.5%), is a byproduct of trinitrotoluene synthesis and is found at production sites. This study explores the effect of ATZ treatment on the bioactivation of the promutagen, 2, 6‐DNT. Male Fischer 344 rats (5 weeks old) were administered 50 mg/kg of ATZ by gavage for 5 weeks. At 1, 3, and 5 weeks, both DMSO‐control and ATZ‐pretreated rats were treated p.o. with 75 mg/kg of 2, 6‐DNT and were housed in metabolism cages for urine collection. Sulfatase‐and β‐glucuronidase‐treated, concentrated urine was bioassayed for urinary mutagens in a microsuspension modification of the Salmonella assay with and without metabolic activation. No significant change in mutagen excretion was observed in ATZ‐treated rats; however, an elevation in direct‐acting urine mutagens from rats receiving ATZ and 2, 6‐DNT at weeks 1 (359 ± 68 vs. 621 ± 96 revertants/ml) and 5 (278 ± 46 vs. 667 ± 109 revertants/ml) of treatment was observed. The increase in production of urinary mutagens was accompanied by an elevation in small intestinal nitroreductase activity. Increases in large intestinal nitroreductase and β‐glucuronidase were observed after 5 weeks. There was no apparent effect of ATZ following 5 weeks of treatment on the production of 2, 6‐DNT‐derived hepatic DNA adducts. ATZ treatment modifies intestinal enzymes responsible for promutagen bioactivation, and potentiates the excretion of mutagenic urine in 2, 6‐DNT‐treated animals. © 1995 Wiley‐liss, Inc.This article i s a US Government work and, as such, i s in the public domain in the United States of America.
Induction of kinetochore‐containing micronuclei by exogenous 06‐methylguanine requires conversion of the methylated base to a nucleotide
Authors: Bonatti Stefania , Aprile Anna , Arena Giuseppe , Cavalieri Zita , Pellerano Paola , Rocco Mattia , Sailer Klaus , Viaggi Silvia , Abbondandolo Angelo 
Published: February 2007

AbstractIt has been reported that exogenous alkylated purines, such as O6‐methylguanine (O6meG), induce aneuploidy in mammalian cells. It is shown here that the aneugenic effect of O6meG, evidenced by its ability to induce micronuclei in rodent cells, is dependent on its conversion to O6‐methyl‐guano‐sine‐5′‐monophosphate (O6me‐5′‐GMP) by hypo‐xanthine‐guanine phosphoribosyl transferase (HPRT). This conclusion, in contrast with previous in vitro data showing that O6meG does not seem to be a substrate for HPRT, was based on the following observations: 1) O6meG did not induce micronuclei in HPRT‐deficient Chinese hamster cells, but did induce micronuclei in HPRT‐proficient cells, and in mouse cells partially or totally deficient in adenine phosphoribosyl transferase; 2) O6meG was not metabolized in HPRT‐deficient cells, while in wild‐type cells a number of metabolites were detected by high performance liquid chromatography (HPLC) analysis of cold acid extracts, one of them coeluting with O6me‐5′‐GMP used as a marker; 3) when de novo synthesis of purine nucleotides was inhibited by aminopterin, O6meG sustained the growth of HPRT‐proficient, but not of HPRT‐deficient, cells; and 4) when HPRT‐deficient cells were treated with lipo‐somes charged with O6me‐5′‐GMP, induction of micronuclei was shown. The finding that methylated guanine exerts its aneugenic action through methylated nucleotide(s) provides an important, though indirect, support to the hypothesis that alkylating agents may induce aneuploidy via nucleotide pool alkylation. © 1995 Wiley‐Liss, Inc.
Energy relaxation method for chemical non‐equilibrium flow computations
Authors: Patil M. M. , Mandal J. C. , Swaminathan S. 
Published: February 2007

AbstractIn this paper, an algorithm for chemical non‐equilibrium hypersonic flow is developed based on the concept of energy relaxation method (ERM). The new system of equations obtained are studied using finite volume method with Harten–Lax–van Leer scheme for contact (HLLC). The original HLLC method is modified here to account for additional species and split energy equations. Higher order spatial accuracy is achieved using MUSCL reconstruction of the flow variables with van Albada limiter. The thermal equilibrium is considered for the analysis and the species data are generated using polynomial correlations. The single temperature model of Dunn and Kang is used for chemical relaxation. The computed results for a flow field over a hemispherical cylinder at Mach number of 16.34 obtained using the present solver are found to be promising and computationally (25%) more efficient. The present solver captures physically correct solution as the entropy conditions are satisfied automatically during the computations. Copyright © 2007 John Wiley & Sons, Ltd.
Secondary nonrandom chromosomal abnormalities of band 13q34 in burkitt lymphoma‐leukemia
Authors: Berger Roland , le Coniat Maryvonne , Derré Josette , Vecchione Danielle 
Published: February 2007

AbstractClonal abnormalities of the long arm of chromosome 13 were detected in 9 of 54 patients with Burkitt lymphoma‐leukemia. All abnormalities involved band 13q34, in three patients as t(1;13). The 13q34 abnormalities are thus the second most frequent secondary chromosomal abnormalities, after those of chromosome 1, in these lymphoid proliferations.