bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytogenetic analyses of mice exposed to dichloromethane
Authors: Allen James , Kligerman Andrew , Campbell James , Westbrook‐Collins Barbara , Erexson Gregory , Kari Frank , Zeiger Errol 
Published: February 2007

AbstractChromosome damage was studied in female B6C3F1 mice exposed to dichloromethane (DCM) by subcutaneous or inhalation treatments. No increase in the frequency of either sister chromatid exchanges (SCEs) or chromosome aberrations (CAs) in bone marrow cells was observed after a single subcutaneous injection of 2,500 or 5,000 mg/kg DCM. Inhalation exposure to DCM for 10 days at concentrations of 4,000 or 8,000 ppm resulted in significant increases in frequencies of SCEs in lung cells and peripheral blood lymphocytes, CAs in lung and bone marrow cells, and micronuclei (MN) in peripheral blood erythrocytes. Lung cell CAs and blood erythrocyte MN reached frequencies of approximately two times control levels. Following a 3‐month inhalation exposure to 2,000 ppm DCM, mice showed small but significant increases in lung cell SCEs and peripheral blood erythrocyte MN. These findings suggest that genotoxicity may play a role in the carcinogenicity of DCM in the lungs of B6C3F1 female mice.
Identification of carcinogenic tryptophan pyrolysis products in human bile by high‐performance liquid chromatography
Authors: Manabe Shigeo , Wada Osamu 
Published: February 2007

AbstractThe carcinogenic tryptophan pyrolysis products 3‐amino‐1,4‐dimethyl‐5H‐pyrido[4,3‐b]indole (Trp‐P‐1) and 3‐amino‐1‐methyl‐5H‐pyrido[4,3‐b]indole (Trp‐P‐2) have been demonstrated to be present in human bile through use of a highperformance liquid chromatography (HPLC) method. The method consists of the acid‐induced release of the carcinogens from bile components and their extraction with methylene chloride and subsequent quantification by HPLC. In seven subjects who had received cath‐eterization of the bile duct and external biliaryd‐rainage, the average amounts of Trp‐P‐1 and Trp‐P‐2 excreted daily in the bile were 408 fmol/ day (n = 7) and 864 fmol/day (n = 7), respectively. In one subject, furthermore, significant daily changes of these carcinogen levels in bile and plasma were confirmed during 2 weeks of observation. These results indicate that one of the excretory pathways of these carcinogens is via bile. Our data also may suggest that Trp‐P‐1 and Trp‐P‐2 are derived from everyday foods.
Colony hybridisation in escherichia coli: A rapid procedure for determining the distribution of specific classes of mutations among a number of preselected sites
Authors: Halliday Jennifer A. , Zielenska Maria , Awadallah Safwat S. , Glickman Barry W. , Skopek T. R. 
Published: February 2007

AbstractColony probe oligonucleotide hybridisation was used for the unambiguous identification of DNA alterations and the determination of distributions and frequencies of forward mutation at the molecular level. To demonstrate the reliability and versatility of this technique, distributions of spontaneous and ethyl methanesulfonate (EMS)‐induced mutations have been reproduced using a battery of oligonucleotide probes complementary to specific sites and classes of mutation. These studies are indicative of the diagnostic potential of oligonucleotide colony hybridisation to the characterisation of mutation; oligonucleotide hybridisation used in conjunction with a well studied mutational target provides a rapid and reliable alternative to DNA sequencing for the characterisation of all classes of mutations.
Effect on SCE in Human chromosomes in vitro of low‐level pulsed magnetic field
Authors: García‐Sagredo J. M. , Parada L. A. , Monteagudo J. L. 
Published: February 2007

AbstractWe analyzed sister chromatid exchanges (SCE) frequencies as an indicator of DNA damage induced in human lymphocytes in vitro by a low‐level pulsed electromagnetic field.We studied the effect of low‐level pulsed electromagnetic fields on human chromosomes with the cytogenetic assay of sister chromatid exchange (SCE) analysis. After the human peripheral lymphocyte cultures were exposed in vitro to the electromagnetic field at different intensities, no significant differences were observed when comparing with the control group as to the number of SCE.
Stability of the mutagenicity in stored cigarette smokers' urine and extract
Authors: Williams R. W. , Watts R. , Inmon J. , Pasley T. , Claxton L. , Einstadt E. 
Published: February 2007

AbstractUrine from cigarette smokers was analyzed for the effect upon mutagenic activity when stored for as long as 175 days. Frozen aliquots of urine were thawed out at various time points in the study and prepared for bioassay. These urine extracts were not bioassayed immediately, but rather refrozen until all of the unprocessed urine samples had eventually been prepared for bioassay. All extracts were obtained using cyanopropyl solid phase extraction techniques. At the end of 175 days, all extracts were bioassayed using a microsuspension assay of Salmonella typhimurium TA98. Urine from smokers was found to be mutagenic (14.4—30.9 revertants/ml equivalent) while a control set of urine from non‐smokers was not. Data from the storage study when analyzed by analysis of variance techniques indicated no statistical loss of mutagens occurred over the 175‐day period although near significance was observed (P = 0.054). This near significance was the result of decreasing mutant response as storage time increased for two of the higher doses tested.
The feasibility of using chinese hamsters as an animal model for aneuploidy
Authors: Sheu Chingju W. , Lee Jung K. , Arras Carol A. , Jones Robert L. , Lavappa Kantharajapura S. , Morgan W. F. 
Published: February 2007

AbstractThe utility of Chinese hamsters as a test species for aneuploidy analysis was studied using four chemicals & mdashvincristine, methyl 2‐benzimidazole carbamate (MBC), nocodazole, and cyclophosphamide. Ten or more male Chinese hamsters were used per dose and bone marrow was removed at intervals of 6—96 hr. Slides were coded and 50—100 metaphases were analyzed per animal. A metaphase with more than 22 chromosomes was classified as a hyperploid cell, and the data were evaluated by using a one‐tailed Fisher's exact test. In experiments using vincristine, MBC, and nocodazole, the frequencies of hyperploid cells were 0.43, 1.14, and 0.91%, respectively, for the control groups. In the experiment using cyclophosphamide, the control value frequency was 3.75%. The treated groups showed no significant increase in hyperploid frequencies when compared to concurrent controls at each of the treated times, except the value at 24 hr for the group that had been treated with vincristine at 0.75 mg/kg. However, this increase was not significant when compared to the overall value for pooled controls, with or without the cyclophosphamide control. Therefore, no significant effects due to chemical treatment were obtained in the present study. The results illustrate the extent of animal‐to‐animal as well as experiment‐to‐experiment variability in hyperploid frequencies and the importance of incorporating concurrent controls in assays for aneuploidy.
Quantitative structure‐activity relationships of heterocyclic amine mutagens formed during the cooking of food
Authors: Hatch F. T. , Knize M. G. , Felton J. S. , Morgan R. W. 
Published: February 2007

AbstractThe major protein‐rich foods, particularly muscle meats, contain part‐per‐billion quantities of potent mutagens formed by frying or broiling to a well‐done state. Related mutagens are formed by pyrolysis of amino acids or proteins and in heated model systems. The thermic mutagens so far identified are heterocyclic aromatic amines of aminoimidazo‐azaarene (AIA) and amino‐carboline classes. The chemicals require activation by enzymes to form metabolites reactive with nucleic acids. These thermic mutagens, and numerous synthetic congeners, exhibit an enormous range of potency as frameshift mutagens in the Ames/Salmonella assay. However, structural variations are nominal within the two classes. Structural parameters that appeared relevant to determining potency were selected for 38 AlAs and 23 amino‐carbolines. For the AlA class these were: the number of fused rings, the number of heteroatoms in Rings 2 and 3, methyl substitution on imidazo ring nitrogen atoms, and methyl substitution on ring carbon atoms. For the amino‐carboline class the structural parameters were: the position of the pyridine‐type nitrogen atom in Ring 1, the substitution position of the exocyclic amino group on Ring 1, and methyl substitution on ring carbon atoms. These structural parameters may influence mutagenic potency in the following ways. 1) Electronic or steric effects may determine the reactivity and stability of the ultimate mutagenic metabolite. Optimal balance of reactivity and lifetime of this transient intermediate may be required for access to and reaction with nuclear DNA to cause mutations. 2) Substitution on the rings may block detoxication reactions. The structural parameters identified should prove useful in predicting the mutagenicity of untested compounds of these types.
Assessment of 1,2‐dimethylhydrazine in bone marrow micronucleus assay: Variations in protocol and response
Authors: Goldberg M. T. , Schop R. N. , Reidy J. A. 
Published: February 2007

AbstractThe effect of variations in experimental protocol on the assessment of the genotoxicity of 1,2‐dimethylhydrazine (DMH) in the bone marrow micronucleus assay was determined. The incidence of micronuclei (MN) in the bone marrow of CBA mice treated with DMH (either intraperitoneally (i.p.) or orally) was found to be significantly greater than that observed in C57B1/6J mice using the same dose and dosing regimen. With i.p. injection, DMH, at doses of 20 and 50 mg/kg, was found to be positive in the bone marrow MN test in CBA mice only. In C57B1/6J mice, DMH (i.p.) was found to be positive at only the 50 mg/kg dose. With oral administration, DMH was positive in the MN test only at the 50 mg/kg dose and only in CBA mice. No significant difference in the percentage of MN was observed when 300,500, or 1,000 polychromatic erythrocytes (PCEs) were scored following a single treatment of DMH. Cyclophosphamide (CY) was found to induce a dose‐dependent increase in the percentage of MN observed in the bone marrow of C57B1/6J mice.DMH tested positive in the colon nuclear aberration (NA) assay in both strains of mice using both i.p. and oral routes of administration, although C57B1/6J mice were found to be more sensitive than CBA mice. No significant difference was observed regarding the percentage of NAs observed in the colon between mice injected i.p. or orally gavaged.
Replication index in cultured human lymphocytes: Methods for statistical analysis and possible role in genetic toxicology
Authors: Lazutka J. R. , Margolin B. H. 
Published: February 2007

AbstractThe replication index (RI) is an index of cytokinetics in cultured cells. This paper presents statistical methods for the analysis of RI data. It also proposes formulas for the calculation of RI and its standard error. The proposed statistical analysis may be applied only in cases when replicate cultures are used. If duplicate or repeated cultures are used, the interculture variation may provide a more suitable error term for RI. Determining the RI in human blood cultures may be useful in genotoxicity testing, because inhibition of DNA synthesis will result in a decrease of the RI. Monte Carlo methods are used to show that the sensivity of the proposed method is roughly equivalent to that of a χ2 test. Power studies indicate that for the study sample, no less than 200 cells should be analyzed when assessing the RI.
Responses of the L5178Y mouse lymphoma cell forward mutation assay. V: 27 coded chemicals
Authors: McGregor Douglas B. , Brown Alison G. , Howgate Susan , McBride Douglas , Riach Colin , Caspary William J. , Carver J. H. 
Published: February 2007

AbstractTwenty‐seven chemicals were tested for their mutagenic potential in the L5178Y tk+/tk− mouse lymphoma cell forward mutation assay using procedures based upon those described by McGregor et al. (McGregor DB, Martin R, Cattanach P, Edwards I, McBride D, Caspary WJ (1987): Environ Mol Mutagen 9:143–160). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 μg/ml. The chemicals were tested at least twice. Statistically significant responses were obtained with acid orange 10, aniline, benzaldehyde, o‐chloroaniline, chlorodibromomethane, cytembena, 1,2‐dibromo‐4‐(1,2‐dibromomethyl) cyclohexane, dieldrin, lithocholic acid, oxytetracycline, phenazopyridine HCl, 1‐phenyl‐3‐methyl‐5‐pyrazolone, sodium diethyldithiocarbamate, solvent yellow 14, tetraethylthiuram disulfide (disulfiram), 2,4‐toluene diisocyanate, and 2,6‐toluene diisocyanate. Apart from phenazopyridine HCl, acid orange 10, and solvent yellow 14, rat liver S9 mix was not a requirement for the mutagenic activity of these compounds. Chemicals not identified as mutagens were N‐4‐acetylaminofluorene, chlorpheniramine maleate, chlorpropamide, 1,4‐dioxane, endrin, ethylene glycol, iron dextran, methapyrilene, sodium(2‐ethylhexyl)alcohol sulfate, and 2,3,7,8‐tetra‐chlorodibenzo‐p‐dioxin.
Analysis of bleomycin‐induced mutagenic functions related to the PSO4 (= XS9) gene of saccharomyces cerevisiae
Authors: Severgnini A. , Lillo O. , Nunes E. , Brockman H. E. 
Published: February 2007

AbstractIn the present work we analyse some properties of the pso4‐1 (= xs9) mutant of the yeast Sac‐charomyces cerevisiae, which is blocked in both reverse mutation and recombination. We have applied the “apparent survival test” as a method to characterize putative inducible errorprone repair activities related to the PSO4 gene. As the mutagenic agent we have used bleomycin, which is an antitumour radiomimetic antibiotic. Survival, reverse mutation yield, and reverse mutation frequency were determined as a function of bleomycin concentrations (1‐60 μg/ml) in the logarithmic phase of growth. It is shown that the PSO4 gene product is poorly involved in bleomycin sensitivity and that reverse mutation induced by this mutagen is dramatically reduced in the pso4‐1 lys2 mutant strain, as compared with the isogenic SC7K (lys2) strain. M(x) functions exhibit linear‐quadratic courses for both the SC7K (lys2) and the pso4‐1 lys2 strains. The apparent survival functions display “humps” in both strains, corresponding to the resistant components of the survival functions. These facts suggest that the mutagenicity of bleomycin depends on at least one inducible error‐prone repair pathway and that the PSO4 gene product could act as a mutation triggering factor.
Sex and strain differences in the hepatocyte primary culture/DNA repair test
Authors: McQueen Charlene A. , Way Barbara M. , Casciano D. A. 
Published: February 2007

AbstractThe hepatocyte primary culture (HPC)/DNA repair test was developed using hepatocytes isolated from male F‐344 rats. A number of genetic polymorphisms have been shown to occur in inbred strains of rats, which may lead to variation in biotransformation of xenobiotics resulting in differences in susceptibility to genotoxins. The effect of the strain utilized as a source of hepatocytes was investigated with female Lewis, F‐344, and DA rats. Variation was observed when hepatocytes from the three strains were exposed to aflatoxin B1 (AFB1). Hepatocytes from female Lewis rats were more sensitive to AFB1 genotoxicity than cells from F‐344 or DA rats. DNA repair was induced by a concentration as low as 108 M AFB 1 in the Lewis strain while 104 M was needed for hepatocytes from female F‐344 or DA rats. Sex‐related differences were also observed with AFB1; DNA repair was induced at 108 M in hepatocytes from male F‐344 rats. No clearcut strain differences were seen when cells were exposed to diethylnitrosamine (DEN) or 2‐acetylaminofluorene, although 102 M DEN was only cytotoxic to hepatocytes from DA rats. These results demonstrate that both the strain and the sex of the animal used as a source of hepatocytes can affect the HPC/DNA repair test.
Frequency of sister chromatid exchange in peripheral lymphocytes of male pesticide applicators
Authors: Rupa D. S. , Reddy P. P. , Sreemannarayana K. , Reddi O. S. , Galloway S. M. 
Published: February 2007

AbstractIn the present study 61 male pesticide applicators who worked in cotton fields and regularly sprayed pesticides such as DDT, BHC, endosulfan, malathion, methyl parathion, phosphamidon, dimethoate, monocrotophos, quinalphos fenvelrate, and cypermethrin were analyzed for sister chromatid exchanges, mitotic index, and cell cycle kinetics in peripheral lymphocytes. Subjects who handled pesticides were non‐smokers and teetotalers and the data were compared with the matched control group. Statistical analysis revealed that the frequency of sister chromatid exchanges was significantly higher among the pesticide applicators at all the durations of exposure when compared to controls. Subjects exposed to pesticides also showed cell cycle delay and decrease in mitotic index when compared to the control group.
A molecular Geneticist's view of complex genomic lesions
Authors: Hozier John C. 
Published: February 2007

AbstractMolecular genetic techniques have been used effectively to study the DNA lesions, many of which are large and complex, that are responsible for human genetic disease. In this workshop we explore some of these techniques, how they are applied to study genetic lesions, and how they may be applied to the needs of genetic toxicology.
Molecular analysis of mutations affecting hprt mRNA splicing in human T‐lymphocytes in vivo
Authors: Rossi Anna M. , Tates Ad D. , Van Zeeland Albert A. , Vrieling Harry 
Published: February 2007

AbstractMolecular analysis of hypoxanthine‐guanine phosphoribosyltransferase (hprt) cDNA from 6‐thioguanine‐resistant T‐lymphocytes cloned from smoking and non‐smoking adult donors showed that 35% of these mutants were defective in splicing of hprt mRNA. Among a set of 42 hprt splice mutants, we observed i) complete loss of one or more exons, ii) partial loss of one exon, or iii) inclusion of part of an intron sequence between adjacent exons. Loss of exon 4 was significantly more frequent than of the other exons, suggesting that the sequences that regulate splicing of this exon are either larger than those of the other exons or especially prone to mutation. In order to identify the molecular nature of DNA alterations causing aberrant splicing of hprt mRNA, 17 splice mutants were analyzed in more detail by sequencing the genomic regions flanking the mis‐spliced exon. Base pair substitutions or small deletions causing defective splicing were either detected in exon sequences or in splice site consensus sequences of introns. Furthermore, genomic deletions encompassing entire exons were found. In some mutants, the alteration responsible for incorrect splicing could not be identified, suggesting that the target sequence for splice mutations is larger than merely the splice junctions. Molecular characterization of hprt splice mutations will lead to the identification of specific sequences regulating splicing of hprt mRNA and will reveal whether the mutational spectrum in splice mutants is similar to that found in the hprt coding region.
Induction of 6‐thioguanine‐resistant mutants in human diploid fibroblasts in vitro with ethylene oxide
Authors: Kolman Ada , Bohušová Tatiana , Lambert B. , Simons J. W. I. M. 
Published: February 2007

AbstractHuman diploid fibroblasts (strain VH‐10) were exposed to the direct‐acting alkylating agent, ethylene oxide (EtO), in vitro, and the frequency of HPRT mutants was evaluated by selection in medium containing 6‐thioguanine. A dose‐dependent increase of the mutant frequency was found in the dose range of 2.5–10 mMh of EtO. The EtO‐induced mutant frequency increased 5–19 times the background frequency at low or moderately toxic doses, which indicates that EtO is a strong mutagen in human fibroblasts in vitro. The mutagenic potency was 9.8 × 10−6 per mMh.
Further evidence for the aneuploidogenic properties of chelating agents: Induction of micronuclei in mouse male germ cells by EDTA
Authors: Russo A. , Levis A. G. 
Published: February 2007

AbstractA micronucleus assay based on cytogenetic analysis of early spermatids (Tates et al.; Mutation Research 121:131–138, 1983) was applied to determine if the chelating agent ethylenedinitrilotetraacetic acid (EDTA) may induce aneuploidy in mouse meiotic cells. Previous results indicated aneuploidogenic activity of EDTA in Drosophila female germ cells (induction of chromosome loss; Zordan et al.: Environ Mol Mutagen 15:205–213, 1990). In the same study, a standard aneuploidy test based on chromosome counting in mouse secondary spermatocytes failed however to show aneuploidogenic properties of FDTA in mouse somatic and germ cells. In the present study the effects of two clastogens, adriamycin (ADM) and mitomycin C (MMC), and of the aneuploidogenic agent chloral hydrate (CH) were also evaluated. All compounds were tested at a single dose level and at two time intervals corresponding to the treatment of diakinesis/metaphase I/metaphase II spermatocytes. The clastogenic potential of the compounds under study was also evaluated, by chromosomal aberration analysis in mouse spermatogonia, in an independent set of experiments. The results obtained indicate that ADM, CH and EDTA are able to induce micronuclei at meiosis. On the contrary, only ADM and MMC induced chromosomal aberrations in mouse spermatogonia. Therefore, the most probable origin of micronuclei produced by CH and EDTA is whole chromosome lagging. These results provide further evidence for the aneuploidogenic properties of these chelating agents.
Interspecies cytogenetic comparisons: Studies with x‐radiation and bleomycin sulfate
Authors: Kligerman Andrew D. , Bryant Miriam F. , Doerr Carolyn L. , Halperin Edward C. , Kwanyuen Puntipa , Sontag Marc R. , Erexson Gregory L. 
Published: February 2007

AbstractA series of in vitro experiments were conducted to determine if there are innate differences in the sensitivity of peripheral blood lymphocytes (PBLs) from different mammalian species to clastogens. Mouse, rat, and human whole blood samples were exposed to either 0, 0.38, 0.75, 1.5, or 3.0 Gy x‐radiation or 0, 5, 10, 20, 40, or 80 (μg/ml bleomycin for 4 hr. Bromodeoxyuridine‐containing cultures were initiated and the PBLs stimulated to divide with phytohemagglutinin. All cultures were harvested following a 3‐hr colcemid treatment. Slides were made and differentially stained, and first‐division metaphases were scored for chromosome aberrations. In the x‐radiation studies human PBLs were significantly more sensitive than mouse PBLs which were in turn more sensitive than rat PBLs as measured by either the total percent aberrant cells or the number of dicentrics. Data from all three species could be fitted to a linear‐quadratic model. Results with bleomycin suggest that the mouse and human PBLs are equally sensitive to the clastogenic effects of bleomycin. Both appeared to be more sensitive than the rat PBLs, but the variation between experiments was such that the results among species were not significantly different. These results indicate that there may be inherent differences in sensitivity among PBLs of mammalian species; however, more studies are needed to determine if the differences presented here hold for other agents.