bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome aberration, sister‐chromatid exchange, proliferative rate index, and serum thiocyanate concentration in smokers exposed to low‐dose benzene
Authors: Major J. , Jakab M. , Kiss Gabriella , Tompa Anna 
Published: February 2007

AbstractCytogenetical endpoints, i.e., chromosome aberration (CA), sister‐chromatid exchange (SCE), and proliferative rate indexes (PRI), were measured in peripheral blood lymphocytes (PBL) of 42 workers exposed occupationally to low‐dose benzene, and of 42 controls. The role of smoking habit as a confounding factor of genotoxic effects caused by occupational low‐dose benzene exposure was also studied. The benzene concentrations in the ambient air samples varied from 3 to 20 mg/m3 (mean: 7 mg/m3). The continuous low‐dose benzene exposure significantly increased the CA and SCE frequencies, but did not influence PRI. Smoking levels were characterized by subjective accounts and by serum thiocyanate concentrations (SCN). CA and SCE were not significantly increased in smokers compared to nonsmokers, but the differences were expressed to a greater extent in the case of measurement of SCN concentrations. Determination of SCN proved to be more objective in the assessment of genotoxic effects of smoking as a confounding factor of occupational low‐dose benzene exposure. © 1994 Wiley‐Liss, Inc.
Comparative investigations of the genotoxic effects of metals in the single cell gel (SCG) assay and the sister chromatid exchange (SCE) test
Authors: Hartmann Andreas , Speit Günter 
Published: February 2007

AbstractSodium arsenite (NaAsO2) and cadmium sulphate (CdSO4) were tested for their ability to induce genotoxic effects in the single cell gel (SCG) assay and the sister chromatid exchange (SCE) test in human blood cultures in vitro. Both metals induced DNA damage in white blood cells that was expressed and detected as DNA migration in the SCG assay. Dose dependent effects were seen for cadmium in concentrations from 5 × 10−4‐5 × 10−3 M and for arsenic in concentrations from 2 × 10−4‐1.5 × 10−3 M. The distribution of DNA migration among cells, a function of dose, revealed that the majority of exposed cells expressed more DNA damage than cells from control cultures and that with increasing length of DNA migration the variability in migration among cells increased as well.Treatment of cells for 2 hr or 24 hr beginning 48 hr after the start of the blood cultures did not increase the SCE frequency in the case of cadmium but caused a small but significant SCE induction with arsenic at the highest concentration. The metal concentrations which could be investigated in the SCE test were much lower due to a strong toxic effect. Metal concentrations which were toxic in the SCE test were without visible effect in the SCG assay. Thus the two endpoints for the determination of genotoxic effects in vitro differed markedly with respect to the detection of genotoxicity induced by metals. These differences and the biological significance of the findings are discussed. © 1994 Wiley‐Liss, Inc.
Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples
Authors: Pool‐Zobel Beatrice L. , Lotzmann Natalie , Knoll Martin , Kuchenmeister Frank , Lambertz Renate , Leucht Ullrich , Schröder Hans‐GÜNther , Schmezer Peter 
Published: February 2007

AbstractTo assess genotoxic burdens from chemicals, it is necessary to relate observations in experimental animals to humans. The success of this extrapolation would be increased by including data on chemical activities in human tissues. Therefore, we have developed techniques to assess DNA damage in human gastric and nasal mucosa (GM, NM) cells. Biopsy samples were obtained during gastroscopy from macroscopically healthy tissue of the stomach or from healthy nasal epithelia during surgery. The specimens were incubated for 30–45 min at 37°C with a digestive solution. We obtained 1.5–8 × 106 GM cells and 5–10 × 105 NM cells per donor, both with viabilities of 80–95%. The cells were incubated in vitro for 1 hr at 37°C with the test compounds added in their appropriate solvents. In GM cells, we studied N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG), sodium dichromate (Na2Cr2O7), nickel sulphate (NiSO4), cadmium sulphate (CdSO4), and lindane. In NM cells, lindane was investigated. Each compound was assessed for DNA damaging activity in cells of at least three different human donor samples using the microgel single cell assay. Similar studies were performed with GM and NM cells obtained from Sprague‐Dawley rats. We have found human GM cells to be more sensitive to the genotoxic activity of MNNG than rat GM cells (low effective concentration [LEC] = 0.16 and 0.625 μg/ml for human and rat, respectively). Human cells were also more sensitive to the cytotoxic/genotoxic activity of NiSO4 (LEC = 5 and 19 μmoles/ml for human and rat, respectively). CdSO4 was genotoxic in human GM cells (LEC = 0.03–0.125 μmoles/ml), whereas no dose‐related genotoxicity was observed in rat GM at concentrations up to 0.5 μmoles/ml. In contrast, approximately equal responses regarding genotoxicity and cytotoxicity were observed in rat and human GM for Na2Cr2O7 (0.25–1 μmoles/ml). Lindane, however, was genotoxic in three out of four rat GM but not in human GM cells (0.5–1 μmoles/ml), whereas it was active in both rat and human NM cells. Together with other recently published in vivo findings, our results with lindane can be interpreted according to a parallelogram approach. In view of possible human exposure situations and the sensitivities of the two target tissues from both species, the data imply that lindane will pose a health risk to humans by inhalation but not by ingestion. © 1994 Wiley‐Liss, Inc.
Micronucleus induction in cytokinesis‐blocked mouse bone marrow cells in vitro following in vivo exposure to x‐irradiation and cyclophosphamide
Authors: Odagiri Youichi , Takemoto Kazuo , Fenech Michael 
Published: February 2007

AbstractA cytokinesis‐block micronucleus (MN) method for the simultaneous but separate measurement of chromosome damage in erythroid and myeloid bone marrow cells is described. MN induction in cytokinesis‐blocked mouse bone marrow cells in vitro following in vivo exposure to x‐ray or cyclophosphamide (CP) was investigated. Immediately after whole body irradiation with acute doses of either 0, 1, 2 or 4 Gy x‐rays, or 2 hr after treatment with either 0, 12.5, 25, or 50 mg CP/kg body weight, bone marrow cells were collected and then cultured in medium supplemented with 3.0 μ/ml cytochalasin B for 24 hr. The binucleated cells were scored in erythroid, myeloid, lymphoid and other cells.The myeloid/erythroid (M/E) ratio was decreased by x‐irradiation or CP treatment in a dose‐dependent manner. The dividing index (DI; binucleated cells/binucleated + mononucleated cells; %) was decreased in both eryth‐roid and myeloid cells in the same manner. Dose‐dependent increases in MN frequency were observed following x‐irradiation in both erythroid and myeloid cells. A similar dose‐dependent MN induction was observed with CP. The MN frequency in myeloid cells was much greater than in erythroid cells (about 4‐fold following 4 Gy exposure, and more than 10‐fold after 50 mg/kg CP). Lymphoid and other cells were not suitable for scoring DI and MN frequency because of insufficient numbers of binucleated cells. These results suggest that micronuclei can be identified in both myeloid and erythroid cells and that myeloid cells are more susceptible to x‐ray or CP‐induced chromosomal damage than erythroid cells as expressed by MN induction. © 1994 Wiley‐Liss, Inc.
Induction of DNA damage by urethane in mouse testes: DNA binding and unscheduled DNA synthesis
Authors: Sotomayor Rene E. , Sega Gary A. , Kadlubar Fred 
Published: February 2007

AbstractThe extent and persistence of DMA damage and repair were investigated in mouse spermatogenic cells exposed in vivo to urethane (ethyl carbamate, EC). Adult male mice exposed to [3H]EC at 10–1,000 mg/kg were sacrificed 12 hr later. EC/metabolite binding to liver and testicular DNA and to sperm heads from the vasa deferentia was measured. Other male mice were exposed to EC at 50–750 mg/kg, and unscheduled DNA synthesis (UDS) induction was investigated in early spermatid stages. Similar experiments were conducted with vinyl carbamate (VC; putative EC metabolite) at 10–75 mg/kg. [3H]EC bound to liver and testicular DNA and to whole sperm heads. Testicular DNA binding increased linearly with dose, although binding was at least 2 orders of magnitude lower than with liver DNA. Sperm head binding also increased linearly with dose. Dose response studies with the UDS assay showed that EC and VC induced a small but significant increase of the UDS response in early spermatid stages. However, the induced UDS responses were quite variable and did not consistently increase with the administered dose. To determine the time kinetics of UDS induction, [3H]dThd was injected at various times after treatment with 500 mg/kg of EC or 60 mg/kg of VC. A slight but significant UDS increase was observed 4 hr after treatment with EC but not with VC. Overall, these results suggest that EC metabolites bind to testis DNA and cause low‐level DNA damage in mouse sper‐matogenic cells. This type of DNA damage apparently does not have significant genetic consequences. © 1994 Wiley‐Liss, Inc.
Molecular models that may account for nitrous acid mutagenesis in organisms containing double‐stranded DNA
Authors: Hartman Zlata , Henrikson Erik N. , Hartman Philip E. , Cebula Thomas A. 
Published: February 2007

AbstractNitrous acid (NA) is often presumed to cause base substitutions in organisms with double‐stranded DNA as a direct consequence of oxidative deamination of adenine and of cytosine residues. Here we summarize evidence indicating that other mechanisms are involved in the case of NA‐induced G/C→A/T transition mutations. We present several models for pathways of NA mutagenesis that may account for our experimental results and overlapping data noted in the literature. One model proposes that the base substitution mutations observed are due to DNA alkylation damage mediated via nitrosation of polyamines and/or other ubiquitous cellular molecules. Other models assume that pre‐disposing lesions, such as G‐to‐G cross‐links, are first formed. The cross‐links are pictured as leading to perturbations in DNA structure that allow subsequent opportunity for NA‐induced deaminations of cytosine residues in their immediate vicinity. The deaminations preferentially result in G/C→A/T transition mutations at sites highly dependent on adjoining base sequence context (i.e., in NA “mutational hotspots”). A final model proposes that NA‐induced G/C→A/T transition mutations arise mainly from oxidative deamination of guanosine residues and not from deamination of cytosine residues in duplex DNA. © 1994 Wiley‐Liss, Inc.
Localization of the xanthine guanine phosphoribosyl transferase gene (gpt) of E. coli in AS52 metaphase cells by fluorescence in situ hybridization
Authors: Michaelis Kevin C. , Helvering Leah M. , Kindig Delinda E. , Garriott Michael L. , Richardson Katherine K. 
Published: February 2007

AbstractThe purpose of this study was to localize the xanthine guanine phosphoribosyl transferase gene (gpt) to a specific chromosome to investigate its proposed autosomal location in the AS52 cell line. AS52 cells are hgprt‐deficient Chinese hamster ovary (CHO) cells which carry a single functional copy of the E. coli gpt gene. Fluorescence in situ hybridization (FISH) and digoxigenin‐labeled probes, as small as 673 bp, were used in an attempt to localize the 456 bp gpt gene to a specific chromosome. Chi‐square analysis of 13 metaphases showed significant labeling on autosomal chromosomes 6 or 7, which are indistinguishable without further banding analysis. Furthermore, a majority of the signals were on the q arm, proximal to the centromere. The data collected supports incorporation of the gpt gene into an acrocentric autosome of the AS52 cell line. © 1994 Wiley‐Liss, Inc.
Reduction of benzene toxicity by toluene
Authors: Plappert U. , Barthel E. , Seidel H. J. 
Published: February 2007

AbstractBDF1 mice were exposed in inhalation chambers to benzene (900 ppm, 300 ppm) and/or toluene (500 ppm, 250 ppm) 6 hr per day, 5 days per week, for up to 8 weeks. Benzene alone induced a slight anemia after 4 and 8 weeks and a reduction of BFU‐E and CFU‐E numbers in the marrow. The coexposure to toluene reduced the degree of anemia. These results confirm previous studies where toluene was found to reduce benzene toxicity. This protective effect was most pronounced when DNA damage was studied in peripheral blood cells, bone marrow, and liver using the single cell gel (SCG) assay. With benzene alone, either with 300 or 900 ppm, a significant increase in DNA damage was detected in cells sampled from all three organs. Toluene alone did not induce a significant increase in DNA damage. The coexposure of benzene and toluene reduced the extent of DNA damage to about 50% of benzene alone. This result is considered a clear indication for a protective effect of toluene on the genetic toxicity of benzene. © 1994 Wiley‐Liss, Inc.
Enhancement of the mutagenicity of amino acid pyrolysates by phthalate esters
Authors: Sato Takahiko , Nagase Hisamitsu , Sato Kayoko , Niikawa Miki , Kito Hideaki 
Published: February 2007

AbstractThe ability of phthalic acid, phthalic acid anhydride, and various phthalate esters to enhance the mutagenicity of many amino acid pyrolysates was observed with the Ames test (Salmonella typhimurium TA98), but not the SOS Chromotest. Phthalate enhancement of the mutagenicity of 4‐nitroquinoline‐1‐oxide, 2‐nitrofluorene, and benzo[a]pyrene was not observed with either test. The mutagenicity‐enhancing ability may be related to the induction of enzymes such as P450IIB, that metabolize amino acid pyrolysates. By quantitative structure activity relationship (QSAR) analysis, a good correlation was observed between the mutagenicity‐enhancing activity of phthalates and their octanol‐water partition coefficients. © 1994 Wiley‐Liss, Inc.
Improved prediction of carcinogenic potencies from mutagenic potencies for chemicals positive in rodents and the ames test
Authors: Bogen Kenneth T. 
Published: February 2007

AbstractMost studies of correlation between logs of mutagenic potency (MP) and cancer potency (CP) have obtained relatively small but statistically significant estimates of correlation (r) and corresponding log‐log slope (b, in Log[CP] = a + b Log[)MP]). But for mutagenic carcinogens, multistage cancer theory predicts that b and r should be highest when MP values best estimate mutation yields per unit dose at concentrations at least as high as those observed to cause cancer in bioassay animals. To test this hypothesis, the correlation of Ames test and rodent cancer potencies was examined for a total number n of 134 chemicals reported as positive in both assays. Values of maximum significant cancer potency (CP, in [mmol/kg‐day]−1) were obtained from a published carcinogenic potency database. Values of maximum mutagenic potency (MP, as revertants per mmol/L‐plate) were estimated from 2,347 sets of Ames test data reported by the NTP mutagenicity testing program, supplemented by similar data newly obtained for ten heterocyclic amines. For compounds with one or more significantly positive MP estimates based on approximately linear Ames test dose‐response data, linear regression of maximum values of Log(CP) on Log(MP) yielded b = 0.27 ± 0.065 and r = 0.39 (P = 0.0001, n = 105), similar to previously reported results for relatively large n. As predicted, when MP values were additionally restricted to include only values estimated from Ames test data approximately linear at corresponding lowest‐TD50 concentrations, similar regressions yielded significantly improved fits (e.g,. b and r = 0.6, P < 10−7, n = 68). Implications of these findings are discussed concerning the quantitative role that mutations like those measured in the Ames test may have in explaining observed cancerbioassay results. © 1995 Wiley‐Liss, Inc.
Relative genotoxic activities of pesticides evaluated by a modified SOS microplate assay
Authors: Venkat J. A. , Shami S. , Davis K. , Nayak M. , Plimmer J. R. , Pfeil R. , Nair P. P. 
Published: February 2007

AbstractThe genotoxic activities of 47 pesticides were determined using a modified SOS microplate assay in which the induction of β‐galactosidase in E. coli PQ37 was used as a quantitative measure of genotoxic activity. The results were compared with those obtained with anethole, curcumin, and capsaicin, a few examples of naturally occurring compounds present in foods. The assays were conducted with pesticides dissolved either in a suitable solvent, such as 10% DMSO in physiological saline or dispersed in sodium taurocholate micelles, to simulate conditions in the small intestine from where these substances are normally absorbed from the diet. 4‐Nitro‐quinoline oxide (4–NQO) served as the reference standard of a direct acting mutagen. In micellar form, 4–NQO and 25 of the 47 pesticides tested showed significantly higher genotoxic activities than when they were tested in an organic solvent. In micellar form the SOS inducing potency of 4–NQO was almost twice as high as in 10% DMSO in physiological saline. In taurocholate micelles, the five most active compounds had activities in the range of 1,234–3,765 units/μmol and in the order of decreasing activities they were ranked as follows: malathion > dichlorvos > lindane > chlordane > endrin. They were significantly less active than 4–NQO (less than 40%). In micellar solution the naturally occurring compounds, anethole, curcumin, and capsaicin gave activities of 4,594, 928, and 809 units/μmol, respectively. These studies show that genotoxicity may depend upon the environment in which cells are exposed to these potential genotoxins. It appears that testing of the more hydrophobic compounds, both synthetic and naturally occurring, are needed. © 1995 Wiley‐Liss, Inc.
Frameshift mutations in salmonella induced by the extracts of medicinal herbs Lannea edulis (sond.) engl. and Monotes glaber sprague
Authors: Sohni Youvraj R. , Davis Cheryl L. , Deschamps Adrian B. , Kale P. G. 
Published: February 2007

AbstractLannea edulis an(d Monotes glaber have been prescribed for various affectations in the traditional medical practice of Zimbabwe and other parts of Africa. Mutagenicity testing using Salmonella typhimurium strains TA97a, TA98, and TA100, indicated that the aqueous extracts of these plants induced frameshift mutations in Salmonella. The extract of L. edulis displayed marginal mutagenicity in strain TA97a while that of M. glaber showed a significant dose‐dependent mutagenicity in both strains TA97a and TA98. There was no mutagenic effect observed in strain TA100. Two other plant extracts, those of Lannea discolor and Dolichos kilimandscharicus, were nonmutagenic in all three strains. © 1995 Wiley‐Liss, Inc.
1‐nitropyrene as a marker for the mutagenicity of diesel exhaust‐derived particulate matter in workplace atmospheres
Authors: Scheepers Paul T. J. , Martens Marty H. J. , Velders Dick D. , Fijneman Peter , Van Kerkhoven Marco , Noordhoek Jan , Bos Rob P. 
Published: February 2007

AbstractThe use of 1‐nitropyrene (1‐NP) as a marker for the occupational exposure to diesel exhaust (DE) mutagens was investigated in workplace atmospheres contaminated with DE from a variety of emission sources, such as power supplies, forklifts, trucks, caterpillar vehicles, trains, ships' engines, and vehicles in city traffic. Total suspended particulate matter was collected by area sampling. The 1‐NP content of acetone extracts of these samples as determined by gas chromatography‐high resolution mass spectrometry varied from 0.080 to 17 μg/g acetone extractable matter, corresponding to air concentrations of 0.012 to 1.2 ng/m3. A sample collected in a rural area contained 0.0017 ng/m3 1‐NP. The mutagenicity of the extracts was tested in the Salmonella typhimurium strains TA98 and TA1538, using the microsuspension assay with and without metabolic activation by an exogeneous metabolizing system (rat liver S9‐fraction). In addition, the S. typhimurium strains YG1021 and YG1024 were used because of their high sensitivity towards the mutagenicity of nitro polycyclic aromatic hydrocarbons. When plotting the mutagenic potency of the air sample extracts as determined in the absence of liver S9 versus the particle‐associated 1‐NP level, a relatively high correlation (r = 0.80–0.91) was observed in all of the S. typhimurium strains. High correlations (r = 0.80–0.93) were also observed when plotting the results of mutagenicity testing after activation by S9 versus the outcome of chemical analysis. These results show that the 1‐NP content of workplace air samples is associated with their mutagenic potency, suggesting that 1‐NP may be used as a marker for occupational exposure to DE‐de‐rived particle‐associated mutagens © 1995 Wiley‐Liss, Inc.
Study design and sample sizes for a lacl transgenic mouse mutation assay
Authors: Piegorsch Walter W. , Margolin Barry H. , Shelby Michael D. , Johnson Amy , French John E. , Tennant Raymond W. , Tindall Kenneth R. 
Published: February 2007

AbstractDesign features that adjust and account for excess variation in a transgenic mouse mutation assay based on a lacl target transgene from E. coli are considered. These features include proper identification of plate, packaging reaction, and animal identifier codes throughout the experimental and analysis phases of the study, “blocking” of exposed and unexposed animals when preparing and plating multiple packaging reactions from the same genomic DNA sample, separating sectored mutant plaques and complete mutant plaques before performing any quantitative analyses, and testing for sources of excess variation attributable to features of the experimental protocol—such as plate‐to‐plate (within packaging reactions), packaging reaction‐to‐packaging reaction (within animals), and animal‐to‐animal (within study). Control and ethylnitrosourea‐treated animal data are presented from a fully designed study in the lacl assay. The study design incorporates many of these experimental principles. Statistical methods to identify excess variability are noted, and the designed study data are used to illustrate the types of variability encountered in practice. A standard statistical test for two‐sample testing is highlighted, from which recommendations are made for sample size selection in future studies. © 1995 Wiley‐Liss, Inc.