bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overview of the workshops on statistical analysis of mutation data from transgenic mice
Authors: Gorelick N. J. , Thompson E. D. 
Published: February 2007

AbstractEarly results from two transgenic mouse mutation assays, Big Blue™ [Kohler SW et al. (1991): Proc Natl Acad Sci USA 88:7958‐7962] and Muta™ Mouse [Myhr BC (1991): Environ Mol Mutagen 18:308‐315], raised questions about appropriate study design and methods for statistical analysis. First, there were a number of potential sources of variability in the technical aspects of the assay. These are ‘how we do it in our laboratory’ differences, which, if not controlled, ultimately make inter‐laboratory comparison of data difficult. Second, separate from the technical sources of variability were a number of study design issues, e.g., how many animals are needed in each treatment group, how many times should the animal be dosed, what is the appropriate expression period for a particular tissue, how many plaques need to be collected from each animal, and so on.To address these questions and to identify and understand the sources of variability in mutation data from these systems, a workshop was held in June, 1992 in Cincinnati, Ohio, USA. A core group of biologists and statisticians discussed possible sources of bias (tissue sampling, phage recovery and transgene recovery), possible sources of variability in mutant frequency (between animals, protocol‐based sources, and design‐based sources) and assay sensitivity. Following two days of discussion on protocol design and assay procedures, three action steps were recommended: (1) compile a data base of existing mutation data in transgenic mice to study its statistical features, (2) develop standard protocols for the mutation assays; and (3) use the standard protocol to generate a large data base of mutant frequencies in liver DNA from untreated mice for statistical study and analysis. This report summarizes the proceedings and recommendations of the workshop. The progress made toward these recommendations was reviewed in a second workshop, held in April, 1993, in Norfolk, Virginia, part of which is the subject of the accompanying paper by Piegorsch et al. To date, a standard protocol has been developed for the Big BlueTM mutagenesis assay and a data base of over 90 million plaques from seven labs using either the Big BlueTM or MutaTM Mouse system has been assembled, including a large data set of spontaneous liver mutant frequencies in the Big BlueTM system. © 1994 Wiley‐Liss, Inc.
Sources of variability in data from alacltransgenic mouse mutation assay
Authors: Piegorsch Walter W. , Lockhart Ann‐Marie C. , Margolin Barry H. , Tindall Kenneth R. , Gorelick Nancy J. , Short Jay M. , Carr Gregory J. , Thompson Edward D. , Shelby Michael D. 
Published: February 2007

AbstractExperimental features of a transgenic mouse mutation assay based on a lacl target transgene from Escherichia coli are considered in detail. Sources of variability in the experimental protocol that can affect the statistical nature of the observations are examined with the goal of identifying sources of excess variation in the observed mutant fractions. The sources include plate‐to‐plate (within packages), package‐to‐package (within animals), and animal‐to‐animal (within study) variability. Data from two laboratories are evaluated, using various statistical methods to identify excess variability. Results suggest only scattered patterns of excess variability, except possibly in those cases where genomic DNA from test animals is stored for extended periods (e.g., > 90 days) after isolation from tissues. Further study is encouraged to examine the validity and implications of this time/storage‐related effect.
Chemical mutagenesis testing in Drosophila. IX. Results of 50 coded compounds tested for the national toxicology program
Authors: Foureman P. , Mason J. M. , Valencia R. , Zimmering S. 
Published: February 2007

AbstractFifty chemicals were tested for mutagenic activity in post‐meiotic and meiotic germ cells of male Drosophila melanogaster using the sex‐linked recessive lethal (SLRL) assay. As in the previous studies in this series, feeding was chosen as the first route of administration. If the compound failed to induce mutations by this route, injection exposure was used. One gaseous chemical (1,3‐butadiene) was tested only by inhalation. Those chemicals that were mutagenic in the sex‐linked recessive lethal assay were further tested for the ability to induce reciprocal translocations. Eleven of the 50 chemicals tested were mutagenic in the SLRL assay. These included bis(2‐chloroethyl) ether, 1,4‐butanediol diglycidyl ether, 1‐chloro‐2‐propanol, dimethyl methylphosphonate, dimethyl morpholinophosphoramidate, dimethyloldihydroxy‐ethylene urea, 2,2‐dimethyl vinyl chloride, hexamethylphosphoramide, isatin‐5‐sulfonic acid (Na salt), isopropyl glycidyl ether, and urethane. Five of these, including 1,4‐butanediol diglycidyl ether, 2,2‐dimethyl vinyl chloride, hexamethylphosphoramide, isopropyl glycidyl ether, and urethane, also induced reciprocal translocations. © 1994 Wiley‐Liss, Inc.
Mutational spectrum of ICR‐191 at the hprt locus in human lymphoblastoid cells
Authors: Taft Sharon A. , Liber Howard L. , Skopek Thomas R. 
Published: February 2007

AbstractHuman TK6 lymphoblasts were treated with the acridine derivative ICR‐191, and mutants at the hprt locus were isolated. Mutant hprt cDNA was reverse‐transcribed from mRNA, amplified by polymerase chain reaction (PCR), and sequenced. Additions of single G:C base pairs (+1 frameshift mutations) in repetitive G:C sequences were found in 82% (32/39) of the mutants. Sixteen of the +1 frameshifts analyzed were located in a single sequence of six consecutive guanine bases in exon 3. The remaining +1 frameshifts occurred at six different GGG sequences (14 mutants) and a single GGGG sequence (2 mutants) in other hprt exons. The repetitive guanine sequences that underwent frameshift mutagenesis were located in both the transcribed and nontranscribed strands of hprt. No single base deletions (‐1 frameshift mutations) were observed. Base substitutions were observed in 13% (5/39) of the clones analyzed and occurred at both G:C and A:T bases. Loss of exon 4 from the cDNA was also observed in 5% (2/39) of the mutants. Hprt mutants containing seven consecutive guanines (produced from a +1 frameshift in a GGGGGG sequence) were treated with ICR‐191 and wild‐type revertants selected in CHAT medium. Revertants were recovered at a frequency of approximately 10−7 and contained the wild‐type sequence (GGGGGG) in all clones analyzed. The observed frequency of ICR‐191‐induced ‐1 frameshift reversion in the GGGGGGG sequence was ∼500‐fold lower than the estimated frequency of +1 frameshifts observed in the wild‐type GGGGGG sequence following the same ICR‐191 treatment. These results suggest that ICR‐191 produces predominantly +1 frameshift mutations at the hprt locus in human cells. © 1994 Wiley‐Liss, Inc.
Polymerase chain reaction‐directed DNA sequencing of bleomycin‐induced “nondeletion”‐Type, 6‐thioguanine‐resistant mutants in chinese hamster ovary cell derivative AS52: Effects of an inhibitor and a mimic of superoxide dismutase
Authors: An Jie , Hsie Abraham W. 
Published: February 2007

AbstractBleomycin‐induced, 6‐thioguanine‐resistant, “non deletion” mutants pretreated with or without either TRIEN (triethylenetetramine), a superoxide dismutase (SOD) inhibitor, or TEMPOL (4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl), a SOD mimic, were analyzed by polymerase chain reaction (PCR)‐directed DNA sequencing in a Chinese hamster ovary (CHO) cell derivative, AS52. Among the 23 bleomycin‐induced mutants, six have 3‐bp 5′‐TGA‐3′ deletions in the region of 366‐371, five have single‐base deletions, seven have base substitutions, three have insertions, and two have possible translocations. Among the 16 bleomycin‐induced mutants pretreated with TRIEN, six have the 5′‐TGA‐3′ deletion (366‐371), two have single‐base deletions, one has a 13‐bp deletion, four have single‐base substitutions, one has a double‐base substitution, and two have insertions. Among the 17 bleomycin‐induced mutants pretreated with TEMPOL, six have the same TGA deletions, two have single‐base deletions, two have single‐base insertions, four have single‐base substitutions, one mutant has a 12‐bp deletion, one has a 13‐bp deletion, and one mutant shows no detectable change in its coding region in the DNA sequence. A possible shift from a ROS‐mediated mutational spectrum to a spontaneous mutational spectrum by TRIEN further indicates that reactive oxygen species play an important role in bleomycin mutagenesis in mammalian cells. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Differential effects of luminol, nickel, and arsenite on the rejoining of ultraviolet light and alkylation‐induced DNA breaks
Authors: Lee‐Chen S. F. , Yu C. T. , Wu D. R. , Jan K. Y. 
Published: February 2007

AbstractWhen Chinese hamster ovary cells were treated with ultraviolet (UV) light or methyl methanesulfonate (MMS), a large number of DNA strand breaks could be detected by alkaline elution. These strand breaks gradually disappeared if the treated cells were allowed to recover in a drug‐free medium. The presence of nickel or arsenite during the recovery incubation retarded the disappearance of UV‐induced strand breaks, whereas the disappearance of MMS‐induced strand breaks was retarded by the presence of arsenite or of luminol, a new inhibitor for poly(ADP‐ribose) synthetase. Luminol, however, had no apparent effect on the repair of UV‐induced DNA strand breaks, and nickel had no effect on the repair of MMS‐induced DNA strand breaks. When UV‐ or MMS‐treated cells were incubated in cytosine arabinofuranoside (AraC) plus hydroxyurea (HU), a large amount of low molecular weight DNA was detected by alkaline sucrose sedimentation. The molecular weight of these DNAs increased if the cells were further incubated in a drug‐free medium. This rejoining of breaks in cells pretreated with UV plus AraC and HU was inhibited by nickel and by arsenite, but not by luminol. The rejoining of breaks in cells pretreated with MMS plus AraC and HU was inhibited by luminol and by arsenite, but not by nickel. These results suggest that different enzymes may be used in DNA resynthesis and/or ligation during the repairing of UV‐ and MMS‐induced DNA strand breaks, and that nickel, luminol, and arsenite may have differential inhibitory effects on these enzymes. © 1994 Wiley‐Liss, Inc.
32P‐postlabelling analysis of DNA adducts in white blood cells of humans exposed to residential wood combustion particulate matter
Authors: Heussen G. A. H. , Bouman H. G. M. , Roggeband R. , Baan R. A. , Alink G. M. 
Published: February 2007

AbstractResidential wood combustion (RWC) in open fireplaces poses a possible health risk because of the emission into the indoor air of mutagenic and carcinogenic compounds. In the present report it was investigated whether this emission leads to enhanced levels of DNA adducts in white blood cells (WBC) of exposed subjects. Under conditions that most likely reflect the Dutch pattern of use of open fireplaces, RWC increased both indoor air mutagenicity and levels of benzo(a)pyrene (B(a)P) and pyrene. The indirect mutagenicity showed a stronger increase than the direct mutagenicity. The increase in indirect mutagenicity was not directly correlated with the increase in the levels of B(a)P and pyrene. 32P‐postlabelling analysis of DNA adducts following nuclease P1 enrichment or butanol extraction revealed low adduct levels. No combustion‐related increase in the amount of adducts was observed. Possible explanations for the lack of correlation between air monitoring data and WBC DNA adduct levels are discussed. © 1994 Wiley‐Liss, Inc.
Comparison of effects of direct‐acting DNA methylating and ethylating agents on inducible gene expression in vivo
Authors: McCaffrey Jennifer , Hamilton Joshua W. 
Published: February 2007

AbstractOur laboratory is interested in whether chemical carcinogen‐induced DNA damage is non‐ran‐domly distributed in the genome, i.e., “targeted,” at the level of individual genes. As one means of investigating this, we have examined whether carcinogen treatment differentially alters the expression of specific genes in vivo. In this study, we have compared the effects of four direct‐acting simple alkylating agents (methyl methanesulfonate, ethyl methanesulfonate, methylnitrosourea, and ethylnitrosourea) on the steady‐state mRNA expression of a model in‐ducible gene, phosphoenolpyruvate carboxyki‐nase (PEPCK), using the chick embryo as a simple in vivo test system. We observed no effect of any of these four carcinogens on the steady‐state mRNA expression of the constitutively expressed β‐actin, transferrin, or albumin genes in chick embryo liver following a single dose of carcinogen. In contrast, these same treatments significantly altered both the basal and inducible expression of the glucocorticoid‐inducible PEPCK gene. These results support the hypothesis that inducible gene expression is a target for the effects of chemical carcinogens in vivo. In addition, the direction, magnitude, and time course of these effects were agent‐specific. Qualitative and quantitative differences in effects between the methylating and ethylating agents and between the methanesulfonates and nitrosoureas were correlated with differences in their specific patterns of DNA adduct formation, suggesting that different DNA lesions have different effects on inducible gene expression.
Variation of mouse oocyte sensitivity to griseofulvin‐induced aneuploidy and meiotic delay during the first meiotic division
Authors: Marchetti Francesco , Mailhes John B. 
Published: February 2007

AbstractThe effects of varying the time of chemical treatment on the induction of areuploidy and meiotic delay in metaphase II (Mll) oocytes were studied by administering 1,500 mg/kg griseofulvin (GF) at 0, 2, 4, 6, or 8 hr after on injection of human chorionic gonadotrophin (HCG). The results show that the oocytes have a different sensitivity to GF‐induced aneuploidy and meiotic delay during the course of meiotic maturation. Although not restricted to a particular period of meiotic maturation, the frequency of aneuploidy was highest (P < 0.05) when GF was given at 2, 4, or 6 hr after HCG. The maximum frequency of hyperploidy (42.4%) occurred at the 4‐hr treatment time. Also, GF treatment resulted in the induction of meiotic delay as demonstrated by ovulated metaphase I (Ml) and polyploid Mll oocytes. The meiotic delay data depict a period of relative resistance between two periods of sensitivity in that the percentages of ovulated Ml oocytes were 53.3, 21.3, 3.5, 6.7, and 25.7 when GF was given at 0, 2, 4, 6, and 8 hr after HCG, respectively. Also, at these treatment times the percentages of polyploid oocytes were 0.6, 1.7, 7.7, 20.1, and 15.4, respectively. Therefore, the oocytes seem to be more sensitive to GF‐induced meiotic delay during the periods preceding and following meiotic spindle assembly. In conclusion, the results demonstrate that the time of chemical treatment influences the frequency of aneuploidy and the degree of meiotic delay. Also, the results emphasize that to thoroughly characterize the aneugenic potential of a specific chemical several treatment times may be needed. © 1994 Wiley‐Liss, Inc.
Etoposide (VP‐16): Cytogenetic studies in mice
Authors: Agarwal Kalpana , Mukherjee Anita , Sen Soumitra 
Published: February 2007

AbstractEtoposide (VP 16‐213), the epipodophyllotoxin derivative that is widely used in the treatment of cancer, forms complexes with DNA‐topoisomerase type llα to exert its cytotoxicity. The drug was evaluated in vivo in Swiss albino mouse bone marrow cells for its ability to induce clastogenicity and sister chromatid exchanges (SCEs). Doses of 5, 10, 15, and 20 mg/kg body weight etoposide given intraperitoneally induced a dose‐dependent significant increase of clastogenicity (Trend test, α ≦ 0.05). The aberrations induced were predominanty chromatid types. The drug shows specificity for S‐phase cells: cells harvested 6 and 12 hr posttreatment showed a significantly increased number of damaged cells and aberrations per cell. Doses of 0.5, 1.0, 2.5, 5.0, and 10.0 mg etoposide/kg body weight induced a dose‐dependent significant induction of SCEs (Trend test, α ≦ 0.05). The minimal effective concentration was 0.5 mg/kg body weight. Etoposide significantly prolonged the cell cycle time at all concentrations tested: 12‐13 hr in treated animals vs. 11 hr in control. The results confirm in vivo cell cycle phase specificity of the drug and further designate etoposide as a potent clastogen and a genotoxic agent in mice. © 1994 Wiley‐Liss, Inc.
Automatic scoring of sister chromatid exchanges by image analysis in a dose response experiment
Authors: García‐Sagredo J. M. , Piper J. , Rutovitz D. , Vaquero J. J. , Vázquez‐Mazariego Yolanda 
Published: February 2007

AbstractA system which automatically selects second division metaphases and then, automatically scores the number of SCEs of each cell is described. In an initial set of experiments, the performance of the components of the system was measured using a data set in which metaphases had been visually classified as either 2nd division or other; and in 2nd division metaphases, every SCE had been marked on a hard copy. SCE scoring had a true positive rate of about 75% and a false positive rate of about 1.5 false SCEs per metaphase analyzed. Second division detection had a true positive rate of 80% and a false positive rate of about 10% of the non‐2nd division cells. Next, the overall system was compared to human visual scoring in a dose‐response experiment by analyzing the effect of mitomycin C on human chromosomes scored visually by two observers and by the fully automatic scoring. Human visual scoring and machine analysis showed similar dose responses, but the variability between them was considerable. © 1994 Wiley‐Liss, Inc.
Correlation between meteorological conditions and mutagenicity of airborne particupate samples in a tropical monsoon climate area from Kaohsiung City, Taiwan
Authors: Lee H. , Su S. Y. , Liu K. S. , Chou M. C. 
Published: February 2007

AbstractKaohsiung is a city of 1.5 million located in the southern part of Taiwan. It has a serious air pollution problem mainly attributable to much industrial and commercial activity. In order to estimate the effects of traffic, season, and meteorological conditions on the mutagenicity of Kaohsiung City's urban ambient particulate matter, 624 airborne particulate samples were collected on a weekly basis from 12 locations for an entire year. The mutagenic potential of acetone extracts of air samples was evaluated by the Salmonella/microsomal test with S. typhimurium TA98 in the presence and absence of S9 mixtures. The air samples from November 1990 showed the highest direct and indirect mutagenicity among the 12 months, whereas those from June and July 1991 had the lowest direct and indirect mutagenic activity, respectively. The mutagenicity showed a good correlation with amounts of the acetone extractable matter of airborne particulates. The meteorological conditions, monthly mean precipitation, and wind speed also showed a good correspondence with mutagenicity. Wind direction and temperature had a moderate relationship. The major mutagenic fractions of air samples that had the highest mutagenic activity in a month were purified using Sephadex LH‐20 column chromatography, and the contents of PAHs, 1‐NP, and DNPs were analyzed by HPLC. The characteristic concentration ratios of PAHs indicated that, for the main pollution sources of airborne particulates from Kaohsiung city, the mobile sources were more important than the stationary ones. The total amounts of 1‐NP and DNPs in airborne particulates seemed to correspond to their mutagenicity. Although the total amounts of 1‐NP and DNPs in the air samples correlated with their mutagenicity, the major mutagenic chemicals in the airborne particulate samples from Kaohsiung City need further investigation. © 1994 Wiley‐Liss, Inc.
Effects of spermine on formation of HGPRT− mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C in V79 chinese hamster cells
Authors: Fiorio R. , Vellosi R. , Bronzetti G. 
Published: February 2007

AbstractSpermine is a polyamine found in bacteria, animal, and plant tissues. It is involved in a variety of biological processes, and its interaction with DMA stabilizes the secondary structure of the double helix. Spermine is one of the first reported antimutagens, reducing the mutation rate in several prokaryotic test systems, while in eukaryotic organisms conflicting results have been obtained. In light of the significant antimutagenic effect of spermine, it is important to evaluate its activity in mammalian cells in culture. The present study was undertaken to evaluate the ability of spermine to suppress the level of HGPRT mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C. Spermine reduced the mutation frequency induced by ethylmethanesulfonate and methylmethanesulfonate but did not affect survival; with mitomycin C survival was reduced but mutation rate was not influenced.
Genotoxic effects of the carbamate insecticide methomyl. I. In vitro studies with pure compound and the technical formulation “Lannate 25”
Authors: Bonatti Stefania , Bolognesi Claudia , Degan Paolo , Abbondandolo Angelo 
Published: February 2007

AbstractThe carbamate insecticide methomyl and the methomyl‐containing technical formulation “Lannate 25” were tested on whole blood human lymphocyte cultures. Both products induced dose‐dependent increases in chromosome aberrations and micronuclei. Lannate 25 induced DNA damage as measured by the alkaline elution assay and hydroxylation of guanine at the C8 position. Sister chromatid exchanges were not increased significantly with either product. Overall, the technical formulation was more active than the pure compound, when compared at similar concentrations of active principle. Moreover, a different ratio of CREST‐positive/CREST‐negative micronuclei was observed with the two products, pure methomyl being relatively more active than Lannate 25 in the induction of CREST‐positive micronuclei. On the basis of these results, previous evaluations of methomyl as a nongenotoxic compound should be reconsidered. © 1994 Wiley‐Liss, Inc.