bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic activation of organic extracts from diesel, coke oven, roofing tar, and cigarette smoke emissions in the ames assay
Authors: Williams Katherine , Lewtas Joellen 
Published: February 2007

AbstractFour environmental emissions samples were ranked by their genotoxic potency in several bioassays. Although the relative potency of a series of automotive emissions (diesel and gasoline) in the Ames assay correlated well with the relative potency in mammalian cell and mouse skin, this was not the case for the coke oven, roofing tar, and cigarette smoke condensate (CSC) emissions. This study examines the role of metabolic activation in determining the difference between a microbial and a mammalian bioassay in ranking the genotoxic potency of these environmental emissions. Uninduced and Aroclor 1254‐induced S9 from both rat and hamster liver were compared as the metabolic activator in the Ames assay with Salmonella typhimurium TA98. The diesel emissions sample was directacting while the other samples required activation. The standard S9 concentration (only Aroclor‐induced rat, approximately 1.25 mg protein/plate) also produced the maximum mutagenic activity. Induced S9s produced higher mutagenic activity than uninduced. The hamster S9 gave significantly higher mutagenic activities than rat S9 for the coke oven and CSC. The relative potency of these four samples was not significantly different between the microbial (Ames), mammalian cell (mouse lymphoma), and tumor initiation (mouse skin) assays. These results suggest that the differences observed between the relative mutagenic activity of these emissions in the mammalian cell and microbial assays was not due to a lack of optimization of the S9 system but may be inherent in the different response of the indicator cells to different chemical classes.
Mutagenesis at the ouabain‐resistance locus of 3.7.2c l5178y cells by chromosomal mutagens
Authors: Amacher David E. , Dunn Emily M. 
Published: February 2007

AbstractChemical mutagens including methyl methanesulfonate, N‐methyl‐N'‐nitro‐N‐nitrosoguanidine, iodomethane, and epichlorohydrin have been classified as “chromosomal mutagens” in the L5178Y/thymidine kinase (TK) gene mutation assay by Clive and coworkers [Mutat Res 59:61–108, 1979; and “The Predictive Value of Short‐Term Screening Tests in Carcinogenicity Evaluation.” Amsterdam: Elsevier/North Holland, pp 103–123, 1980] who observed mutagen‐dependent increases in small TK‐deficient mutant colonies with detectable damage to the chromosome (11) that carries the TK locus. In this study, we tested these four chemicals for the induction of gene mutations at the ouabain‐resistance (ouares) locus of 3.7.2C L5178Y cells to determine if presumptive chromosomal mutagens would go undetected at a gene locus that is unresponsive to chromosomal damage. A final concentration of 375 μg/ml ouabain in soft‐agar medium selected against the ouabain‐sensitive phenotype without loss of the mutagen‐induced ouabain‐resistant phenotype. Verification of the mutant phenotype was completed for six individual soft‐agar ouares colonies derived from mutagen‐treated cultures via growth for 10–11 days in nonselective medium followed by retesting for colony formation in selective soft‐agar medium. Dose‐related reproducible increases in the frequency of ouabain‐resistant mutants were observed for 3.7.2C L5178Y cells that had been exposed for 3 hr to 24–46 μg/ml epichlorohydrin, 1.9–3.6 μg/ml iodomethane, 0.006–0.011 μg/ml N‐methyl‐N'‐nitro‐N‐nitrosoguanidine and 2.0–5.4 μg/ml methyl methanesulfonate. Also, treatments with EMS, which induced sufficient numbers of ouares colonies to permit analysis of colony size distribution, showed the existence of a bimodal size distribution similar to those reported for TK‐deficient mutants. This discovery suggests that mutant colony size in this cell line may be independent of specific gene locus effects. We conclude that (1) chemicals that induce a high proportion of chromosomal mutants, as detected at the TK locus in earlier studies, also induce single gene mutations at the ouabain‐resistance locus and (2) a bimodal distribution of mutant colony sizes in soft‐agar.
Genetic drift and seasonal variation in spontaneous mutation frequencies in Drosophila
Authors: Mason J. M. , Valencia R. , Woodruff R. C. , Zimmering S. 
Published: February 2007

AbstractSpontaneous sex‐linked recessive lethal mutation frequencies may vary with time. Examination of approximately 1.7 × 106 Drosophila melanogaster × chromosomes in three laboratories suggests two sources of variation in the spontaneous mutation frequency. First, the underlying mutation rate may change with time, suggesting genetic drift among the genes controlling the spontaneous mutation rate. In one set of experiments, the recessive lethal frequency increased from 0.2% to 0.4% in 6 years. Second, there may be seasonal variation in the mutation frequency even under apparently controlled conditions, suggesting that uncontrolled environmental factors may play an important role in determining the mutation frequency. Therefore, concurrent controls should be used in mutation experiments except in cases in which the frequency in the untreated control is so low as to be unmeasurable in a single experiment or the control frequency can be shown not to vary with time.
Significance of the genotoxic activities observed in vitro for 35 of 70 NTP noncarcinogens
Authors: Ashby John , Purchase I. F. H. 
Published: February 2007

AbstractA speculative analysis is presented of the in vitro genotoxicity data reported by Shelby and Stasiewicz for 70 chemicals defined as noncarcinogenic to rodents by the National Toxicology Program. It is concluded that the genotoxic activities observed are probably subject to logical explanation. It is suggested that short‐term genotoxicity assays conducted in vivo on newly defined in vitro genotoxins may have a useful role to play in discriminating animal carcinogens from noncarcinogens. It is clear from the results reported that genotoxic activities observed in vitro for a new test chemical only provide evidence of its possible animal carcinogenicity; they are not definitive of carcinogenicity—the difference may be negligible in general but might prove unacceptable in the particular.
Studies in comparative chemical mutagenesis
Authors: Sobels F. H. 
Published: February 2007

AbstractThis paper presents a review of various collaborative studies in comparative mutagenesis. The following studies are briefly described: (1) the chemical mutagenesis programme of the European Community, (2) Drosophila studies with various alkylating agents of different s (Swain‐Scott) factors, (3) the evaluation by the International Commission for Protection against Environmental Mutagens and Carcinogens (ICPEMC) Committee 1, (4) the Environmental Protection Agency's Gene‐Tox Programme, (5) the first and second United Kingdom Environmental Mutagen Society (UKEMS) collaborative studies, and (6) the International Programme on Chemical Safety (IPCS) collaborative study on in vitro tests. The need for chemical dosimetry is emphasized. One of the main conclusions is that, of the mammalian point mutation assays, the L5178Y (TFTR, trifluorothymidine resistant) system showed greatest detection capability in the second UKEMS study. The consensus conclusion of the IPCS in vitro study was that chromosomal aberrations are considered to be the optimal assay for complementing the Salmonella assay and offer the additional advantage that aneuploidy, polyploidy, and sister chromatid exchanges can also be easily assessed.
Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test
Authors: Tomkins Darrell J. , Wei Lan , Laurie Karen E. 
Published: February 2007

AbstractIt has been shown that circulating peripheral blood lymphocytes can be used for the enumeration of 6‐thioguanine‐resistant cells that presumably arise by mutation in vivo. This somatic cell mutation test has been studied in lymphocytes from human populations exposed to known mutagens and/or carcinogens. The sensitivity of the test could be further enhanced by including other gene markers, since there is evidence for locus‐specific differences in response to mutagens. Resistance to diphtheria toxin (Dipr) seemed like a potential marker to incorporate into the test because the mutation acts codominantly, can readily be selected in human diploid fibroblasts and Chinese hamster cells with no evidene for cell density or cross‐feeding effects, and can be assayed for in nondividing cells by measuring protein synthesis inhibition. Blood samples were collected from seven individuals, and fresh, cryopreserved, or Epstein‐Barr virus (EBV)‐transformed lymphocytes were tested for continued DNA synthesis (3H‐thymidine, autoradiography) or protein synthesis (35S‐methionine, scintillation counting). Both fresh and cryopreserved lymphocytes, stimulted to divide with phytohemagglutinin (PHA), continued to synthesize DNA in the presence of high doses of diphtheria toxin (DT). Similarly, both dividing (PHA‐stimulated) and nondividing fresh lymphocytes carried on significant levels of protein synthesis even 68 hr after exposure to 100 flocculating units (LF)/ml DT. The findings were confirmed in cord blood lymphocytes, ruling out the possibility that diphtheria immunization could have led to a selection of Dipr lymphocytes. One lymphoblast line (EBV‐transformed lymphocytes) showed a reduction in protein synthesis to 0.2% of controls only at 192 hr after exposure to 100 LF/ml. The results suggest that human T and B lymphocytes may not be as sensitive to DT protein synthesis inhibition as human fibroblast and Chinese hamster cells. For this reason, Dipr may not be a suitable marker for the somatic cell mutation test.
Induction of micronuclei in maize root‐tip cells and a correlation with forward mutation at the yg2 locus
Authors: Wagner Elizabeth D , Plewa Michael J. 
Published: February 2007

AbstractA standard protocol for a micronucleus assay in root tips of Zea mays was developed and calibrated using 137Cs gamma radiation, ethylmethanesulfonate (EMS), and N‐ethyl‐N‐nitrosourea (ENU). The root tips were sampled 1, 3, and 5 days after the treatment period. Primary root tips (sampled 1 day after treatment) were the most responsive with the highest frequencies of micronuclei. The frequencies then decreased to control values after 3 days. By treating the same kernels for this assay and the yellow‐green‐2 (yg2) forward mutation assay, it was possible to analyze and compare the induction kinetics of micronuclei formation in root‐tip cells and forward mutation at the yg2 locus in leaf primordial cells. Forward mutation at the yg2 locus by gamma rays, EMS, or ENU exhibited one hit kinetics. The induction of micronuclei demonstrated nonlinear kinetics with a significant increase over controls above 200 rads gamma rays, 10 mM EMS, or 250 μM ENU. ENU induced a higher frequency of micronuclei at all treatment concentrations than did gamma radiation or EMS. The data suggest that a higher relative proportion of yg2 mutant sectors induced by ENU may be due to chromosome aberrations than those induced by gamma radiation or EMS.
The reproductive effects assessment group's report on the mutagenicity of 1,3‐butadiene and its reactive metabolites
Authors: Rosenthal Sheila L. 
Published: February 2007

AbstractA major data gap for assessing heritable risk from exposure to 1,3‐butadiene is the lack of mammalian mutagenicity data. The data base on the mutagenic potential of 1,3‐butadiene is limited to three bacterial studies from the same laboratory. Two of these studies were positive only in the presence of liver S9 mix from chemically pretreated animals. In vitro data suggest that 1,3‐butadiene is metabolized to two epoxide intermediates. 3,4‐Epoxybutene, one potential reactive metabolite of 1,3‐butadiene, is a monofunctional alkylating agent and is a directacting mutagen in bacteria. In addition, unpublished data suggest that 3,4‐epoxy‐butene induces DNA damage and chromosomal aberrations in mice. Another potential reactive metabolite, 1,2:3,4‐diepoxybutane, is a bifunctional alkylating agent and is mutagenic in a wide variety of organisms (bacteria, fungi, and the germ cells of Drosophilo). This metabolite also induces DNA damage in mice and in cultured hamster cells, is clastogenic in fungi and cultured rat cells, and produces chromosome damage/breakage in Drosophila germ cells. These data, when combined with evidence that 1,3‐butadiene is carcinogenic in rodent gonadal tissues and is associated with gonadal atrophy in mice, constitute suggestive evidence that 1,3‐butadiene may be a human germ cell mutagen. However, because the mutagenicity of 1,3‐butadiene has been studied only in bacteria, studies in mammalian test systems are needed to further characterize the mutagenic potential of 1,3‐butadiene.
An interlaboratory comparison of transformation in syrian hamster embryo cells with model and coded chemicals
Authors: Tu A. , Hallowell W. , Pallotta S. , Sivak A. , Lubet R. A. , Curren R. D. , Avery M. D. , Jones C. , Sedita B. A. , Huberman E. , Tennant R. , Spalding J. , Kouri R. E. 
Published: February 2007

AbstractThree independent laboratories tested eight “model” and five coded chemicals in the Syrian hamster embryo clonal transformation assay system to establish the intra‐ and interlaboratory reproducibility of the system and to identify sources of variability. When a common cell pool and the same lot of fetal calf serum were used, the three laboratories obtained consensus on the activity of eight model chemicals: five chemicals (benzo(a)pyrene, 7,12‐dimethylbenz(a)anthracene, N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, nitroquinoline‐N‐oxide, and lead chromate) induced morphological transformation without exogenous metabolic activation and three (N‐2‐fluorenylacetamide, pyrene, and anthracene) produced no transformation response. Five coded chemicals (2,6‐dichloro p‐phenylenediamine, 4,4′‐oxydianiline, cinnamyl anthranilate, dichlorvos, and reserpine), representative of environmental chemical classes, but not necessarily strong carcinogens, produced more equivocal responses in this interlaboratory study. Thus, while the assay can be used to distinguish between transforming and nontransforming chemicals in some cases, the intrinsic limitations in low transformation frequency and in achieving any dose‐response results are major constraints to the use of this systsem in a routine testing program at the present time. Efforts to increase the transformation frequency or to amplify the expression of the transformed phenotype constitute some of the approaches which should be explored in order to overcome these limitations.
The reproductive effects assessment group's review of the mutagenicity of vinylidene chloride
Authors: Jacobson‐Kram David 
Published: February 2007

AbstractA large number of studies indicate that vinylidene chloride is mutagenic to bacteria and that this activity is largely dependent on microsomal activation. Vinylidene chloride gave positive results for gene reversion and conversion in yeast that was also dependent on metabolic activation, and was positive in tradescantia. In mammalian systems, vinylidene chloride failed to induce gene mutations in V79 cells at two separate loci, failed to induce chromosomal aberrations in mouse bone marrow in vivo, and failed to induce dominant lethals in either mice or rats. Vinylidene chloride was found to alkylate DNA of mice exposed through inhalation and may have caused unscheduled DNA synthesis in kidneys of similarly exposed mice. The studies on the mutagenicity of vinylidene chloride are evaluated in this review.
The genetic toxicology of metal compounds: II. Enhancement of ultraviolet light‐induced mutagenesis in escherichia coli WP2
Authors: Rossman T. G. , Molina M. 
Published: February 2007

AbstractSalts of metals which are carcinogenic, noncarcinogenic, or of unknown carcinogenicity were assayed for their abilities to modulate ultraviolet (UV)‐induced mutagenesis in Escherichia coli WP2. In addition to the previously reported comutagenic effect of arsenite, salts of three other compounds were found to enhance UV mutagenesis. CuCl2, MnCl2 (and a small effect by KMnO4), and NaMoO4 acted as comutagens in E coli WP2, which has wild‐type DNA repair capability, but were much less comutagenic in the repair deficient strain WP2s (uvrA). The survival of irradiated or unirradiated cells was not affected by these compounds. No effects on UV mutagenesis were seen for 16 other metal compounds. We suggest that the comutagenic effects might occur either via metal‐induced decreases in the fidelity of repair replication or (in the case of CuCl2) via metal‐induced depurination.
Sister chromatid exchange induction and persistence in peripheral blood and spleen lymphocytes of mice treated with ethylnitrosourea
Authors: Tucker James D. , Strout Cheryl L. , Christensen Mari L. , Carrano Anthony V. 
Published: February 2007

AbstractThe induction and persistence of sister chromatid exchanges (SCEs) were studied in peripheral blood and spleen lymphocytes of mice given a single i.p. injection of ethylnitrosourea (ENU) of 100, 350, or 600 μMoles ENU/kg. SCE frequencies were measured on days 1, 3, 5, and 7, and at seven additional times up to 172 days post‐injection. SCEs were analyzed statistically by comparing the mean frequencies as well as the distribution of SCEs per cell at each time. The latter approach was based on a non‐parametric method of identifying high frequency cells (HFCs). The SCE frequencies and proportion of HFCs in each dose and tissue remained elevated for up to 172 days following treatment, although the degree and statistical significance of the increase varied according to the tissue, dose, and statistical test employed. The SCE frequencies were found to oscillate during the first week. Following this, however, the return of the SCE frequencies to control levels was fit to a linear regression model with time as the only independent variable. The persistence of SCE‐forming lesions was found to be dose‐dependent for the spleen but not for blood. Within each dose the persistence of SCE‐forming lesions was significantly greater for the blood relative to the spleen. The results emphasize that 1) tissue, dose, and time since exposure are important factors to consider when quantifying SCEs in vivo; 2) analysis of high frequency cells may be a more sensitive method of detecting exposure than the t‐test; and 3) a single determination of SCE frequencies may not be sufficient to quantitatively assess genotoxic damage in the first week following exposure.
Reactivity of mutagenic propylene oxides with deoxynucleosides and DNA
Authors: Djuric Z. , Hooberman B. H. , Rosman L. , Sinsheimer J. E. 
Published: February 2007

AbstractIn an extension of previous studies with deoxycytidine and thymidine reactivities, propylene oxide, glycidol, epichlorohydrin, and trichloropropylene oxide were reacted with deoxyguanosine as well as deoxyadenosine and, except for the trichloro compound, with DNA. Reactivity with the purine deoxynucleosides as well as the four deoxynucleosides in DNA were quantitated by HPLC methods. Correlations were found for the reactivity with individual deoxynucleosides in solution to Taft σ* electron‐withdrawing values of the substituents on the epoxides and for reaction with model nucleophiles. In general, these correlations were not as pronounced for the reactivities of the propylene oxides with the nucleosides in DNA. Correlations for reactivity of the propylene oxides with the individual deoxynucleosides in solution and in DNA, except for dThd, were indicated for mutagenicity in TA100 in the liquid‐preincubation Ames test. However, this was not the case for mutagenicities determined with the plate incorporation procedure nor with TA1535, where the relative mutagenicity of trichloropropylene oxide was the outstanding difference. Trichloropropylene oxide appeared to depend upon the error‐prone system in TA100 for full expression of its mutagenicity.
Sister chromatid exchange and chromosome aberration analyses in mice after in vivo exposure to acrylonitrile, styrene, or butadiene monoxide
Authors: Sharief Y. , Brown A. M. , Backer L. C. , Campbell J. A. , Westbrook‐Collins B. , Stead A. G. , Allen J. W. 
Published: February 2007

AbstractThe use of polymers in plastic and rubber products has generated concern that monomers potentially active in biological systems may be eluted from these substances. We have evaluated two such monomers, acrylonitrile and styrene, for the induction of chromosome damage in mice. Butadiene monoxide, a presumed metabolite of a third important monomer, 1,3‐butadiene, was also tested. These chemicals were administered as a single intraperitoneal injection; sister chromatid exchanges and chromosome aberrations were analyzed in bone marrow cells. Acrylonitrile and styrene were largely negative for these endpoints when tested at doses ranging to 60 mg/kg and 1,000 mg/kg, respectively. Butadiene monoxide, which previously has not been tested in a mammalian system, was determined to be a very effective inducer of sister chromatid exchanges and chromosome aberrations. Both endpoints showed a clear dose response and a greater than ten‐fold increase over control levels at high doses. These studies represent an initial step in our efforts to evaluate genetic risk associated with exposure to common polymeric chemicals.