bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micronuclei formation in somatic cells of mice exposed to 50‐Hz electric fields
Authors: El Nahas Soheir M. , Oraby Hanaa A. 
Published: February 2007

AbstractMale Swiss mice are tested under uniform 50‐Hz electric field intensities of 100, 170, 220, and 290 kV/m. These values on the basis of equal induced current density are equivalent to the case of a human exposed to field intensities of nearly 8, 14, 18, and 24 kV/m, respectively. The latter values may be found beneath or in vicinity of extra‐high‐voltage power lines whose voltages range from 220 to 765 kV. The cytogenetic effect of extremely low‐frequency (ELF) electric fields, as expressed by micronuclei formation, is assessed. Mice are exposed for 24 hr, and samples are taken 48, 72, and 96 hr from the beginning of exposure. Sham‐exposed mice served as controls. The number of micronucleated polychromatic erythrocytes (PCE) in exposed animals are significantly higher than those of the control. The increase in micronucleated PCE was significantly dose dependent at all times. Samples taken 96 hr after exposure show a decrease in percentages of micronucleated PCE, which may be taken as an indication of recovery.
Role of nitroreduction in the synergistic mutational response induced by mixtures of 1‐ and 3‐ nitrobenzo[a]pyrene in Salmonella typhimurium
Authors: Thornton‐Manning Janice R. , Campbell Warren L. , Hass Bruce S. , Chen James J. , Fu Peter P. , Cerniglia Carl E. , Heflich Robert H. 
Published: February 2007

AbstractPrevious studies showed that binary mixtures of the environmental pollutants 1‐ and 3‐nitrobenzo[a]pyrene produced a synergistic mutational response in the Salmonella reversion assay. Since nitroreduction is believed to mediate the direct‐acting mutagenicity of the individual compounds, we have examined the role of nitroreduction in the mutagenicity of mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene in the Salmonella plate incorporation assay. While mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene induced up to 183% more revertants in strain TA98 than produced by equivalent amounts of the individual compounds, in the nitroreductase‐deficient strain TA98NR the same mixtures only induced up to 57% more revertants than the individual compounds. Analysis of mixtures of 1 ‐ and 3‐nitrosobenzo[a]pyrene (the two‐electron reduction products of 1 ‐ and 3‐nitrobenzo[a]pyrene) for mutation induction in TA98 yielded no evidence of a synergistic effect between the compounds. The mutagenicity of the mixtures was dependent upon the amount of the more mutagenic component.Salmonella cultures were also incubated with mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene, as well as with equivalent amounts of the individual compounds. In two experiments, nitroreductive ability, as measured by the amount of 1 ‐nitropyrene metabolized to 1 ‐aminopyrene in 1 hr, was increased 9 to 105% in cultures pretreated with the mixtures as compared with cultures pretreated with the individual compounds. The results of this study support the hypothesis that nitroreduction is a major factor in the synergistic mutational response induced by 1 ‐ and 3‐nitrobenzo[a]pyrene in Salmonella typhimurium.
Rapid detection of DNA‐interstrand and DNA‐protein cross‐links in mammalian cells by gravity‐flow alkaline elution
Authors: Hincks Jeffrey R. , Coulombe Roger A. 
Published: February 2007

AbstractAlkaline elution is a sensitive and commonly used technique to detect cellular DNA damage in the form of DNA strand breaks and DNA cross‐links. Conventional alkaline elution procedures have extensive equipment requirements and are tedious to perform. Our laboratory recently presented a rapid, simplified, and sensitive modification of the alkaline elution technique to detect carcinogen‐induced DNA strand breaks. In the present study, we have further modified this technique to enable the rapid characterization of chemically induced DNA‐interstrand and DNA‐protein associated cross‐links in cultured epithelial cells. Cells were exposed to three known DNA cross‐linking agents, nitrogen mustard (HN2), mitomycin C (MMC), or ultraviolet irradiation (UV). One hour exposures of HN2 at 0.25, 1.0, and 4.0 μM or of MMC at 20, 40, and 60 μM produced a dose‐dependent induction of total DNA cross‐links by these agents. Digestion with proteinase K revealed that HN2 and MMC induced both DNA‐protein cross‐links and DNA‐interstrand cross‐links. Ultraviolet irradiation induced both DNA cross‐links and DNA strand breaks, the latter of which were either protein and nonprotein associated. The results demonstrate that gravity‐flow alkaline elution is a sensitive and accurate method to characterize the molecular events of DNA cross‐linking. Using this procedure, elution of DNA from treated cells is completed in 1 hr, and only three fractions per sample are analyzed. This method may be useful as a rapid screening assay for genotoxicity and/or as an adjunct to other predictive assays for potential mutagenic or carcinogenic agents.
Genetic profile of a nalidixic acid analog: A model for the mechanism of sister chromatid exchange induction
Authors: Holden Henry E. , Barett John F. , Huntington Channing M. , Muehlbauer Paula A. , Wahrenburg Margitta G. 
Published: February 2007

AbstractIn recent years, evidence has accumulated that suggests that mammalian topoisomerase may play a role in the formation of spontaneous or chemically induced sister chromatid exchange (SCE). In microbial systems, nalidixic acid is known to disrupt the function of a topoisom‐erase‐like enzyme, DNA gyrase. To explore the possible relationship to topoisomerase function and SCE formation in mammalian cells, an analog of nalidixic acid with potent topoisomerase II inhibitory activity was selected for examination in a variety of genetic toxicology assays. This analog, CP‐67, 015, proved to be a positive direct‐acting mutagen in the L5178Y/TK+/‐, CHO/ HGPRT, and V79/HGPRT systems. However, no gene mutational activity was observed using the Ames test in direct plate, mouse and rat metabolic activation, and mouse urine tests. In vitro cytogenetic studies showed strong clastogenic activity in human lymphocytes and in CHO cells. Compound‐induced chromosome damage was also observed in vivo in mouse bone marrow cells. Surprisingly, SCE studies in vitro in human lymphocytes or CHO cells showed only slight increases, even at levels producing severe chromosome breakage. Mouse bone marrow showed no significant elevation of SCE following parenteral treatment with CP‐67, 015.These results, taken together, demonstrate that CP‐67, 015 is a direct‐acting mutagen in mammalian cells with both gene and chromosomal level effects. The relative ineffectiveness in producing SCEs suggests that CP‐67, 015 may interfere with a DNA replicative/repair process, perhaps by alteration of one or more DNA polymerase activities. This suggestion is based in part on the known effect of the analog nalidixic acid on DNA gyrase in microbial cells and on topoisomerase in mammalian cells. The profile of genetic activity of CP‐67, 015, coupled with its inhibitory effect on topoisomerase function, gives rise to a model for SCE formation that is based on anomalies of topoisomerase activity during DNA synthesis.
Toxic effects of methyl methanesulfonate (MMS) on activated macrophages from chickens
Authors: Qureshi Muquarrab A. , Bloom Stephen E. , Hamilton Joshua W. , Dietert Rodney R. 
Published: February 2007

AbstractAdherent peritoneal exudate cells rich in macro‐phages were harvested from Cornell K‐strain chickens 42 hr after i.p. stimulation with Sephadex G‐50. Glass‐adherent monolayers were obtained on coverslips and subjected to in vitro exposure to methyl methanesulfonate (MMS) at various doses for 1 hr. Solvent (0.17% ethanol final concentration) and sham (RPMI 1640 growth media) exposures were also performed. At selected times after exposure, the macrophages were analyzed for cell viability, adherence, DMA damage, and functional activity. Although MMS doses of 5 × 10−3 M and 1 × 10−3 M concentrations resulted in significant cytoxicity, 2 × 10−4 M had no significant cytotoxic effect. However, this exposure resulted in DNA damage as measured by alkaline elution. Concomitant with the DNA damage was a significant decrease in the phagocytic activity of macrophages. Repair of MMS‐induced DMA lesions in macrophages was indicated by a normal DNA alkaline elution profile 10 hr postrecovery. Functional activity of cells also returned to normal levels. In contrast, the incidence of Fc receptor‐positive cells detected by rosetting increased immediately after MMS exposure, and phagocytosis of opsonized SRBCs was not affected by 2 × 10−4 M MMS treatment. Similarly, MMS treatment did not alter the acid phosphatase activity of macrophages. However, bactericidal ability of MMS‐treated macrophages for unopsonized Escherichia coli was significantly depressed. These results suggest that the avion macrophage is a useful target cell for examining possible relationships between genotoxic and immunotoxic effects of environmental mutagens.
Genotoxicity of azidoalanine in mammalian cells
Authors: Arenaz P. , Hallberg L. 
Published: February 2007

AbstractSodium azide mutagenesis is mediated through a metabolic intermediate in bacteria and plant species. However, very little is known about the interaction of this intermediate with nucleic acids, its genotoxic potential, or its mechanism of action, especially in mammalian cells. Chinese hamster cells and normal human skin fibroblasts were treated with extracts from Salmonella typhimurium or Hordeum vulgare (barley) containing a crude mutagenic metabolite, as well as with synthetically produced azidoalanine. The cells were evaluated for the induction of sister chromatid exchanges and the ability to perform unscheduled DNA synthesis. With the purified azidoalanine and the azide‐treated extracts from Hordeum vulgare, there was a statistically significant increase in the frequency of sister chromatid exchanges observed in both Chinese hamster cells and human fibroblasts. This increase was about twofold, as compared with the control. On the other hand, there was no detectable genotoxic response when cells were exposed to azide‐treated extract from Salmonella typhimurium. The results imply that azidoalanine and the crude mutagenic metabolite from Hordeum vulgare are weakly genotoxic in mammalian cells.
Flow cytometric analysis of bromodeoxyuridine‐induced inhibition of cell proliferation in the human teratocarcinoma‐derived cell line, p3
Authors: Morris Suzanne M. , McGarrity Lynda J. , Domon Olen E. , Hinson William G. , Kodell Ralph L. 
Published: February 2007

AbstractWe have developed methods in our laboratory whereby the effects of toxicant exposure on cell proliferation can be evaluated flow cytometrically. We sought to relate the flow cytometric analyses to other biological response measurements. Thus, we exposed P3 cells to increasing concentrations of bromodeoxyuridine (BRdU) and measured sister‐chromatid exchange (SCE) frequency, average generation time (AGT), and relative cloning ability. Each of these is well documented (see introduction) to respond to BRdU exposure in a concentration‐dependent manner. In this study, SCE frequency remained constant between the concentrations of 2.5 and 10 μM of BRdU. However, a small, but significant, increase in SCE frequency was observed between the concentrations of 10 μM and 50 μM BRdU. A significant increase in AGT was noted in 50 μM BRdU‐exposed cells. Relative cloning efficiency decreased in a concentration‐dependent manner when cells were cultured for 24, 48, or 72 hours with BRdU. When cell proliferation was assessed by flow cytometric analysis in cells exposed to 0, 10, or 50 μM BRdU, a statistically significant delay in the cell‐cycle was observed in BRdU‐exposed cells. These results may be interpreted to mean that inhibition of cell proliferation is detected by this type of analysis at toxicant concentrations that induce other biological endpoints. The inclusion of flow cytometric analysis in a test battery to evaluate toxicant effects is warranted.
Molecular analyses of in vivo hprt mutations in human t‐lymphocytes: IV. Studies in Newborns
Authors: McGinniss Matthew J. , Nicklas Janice A. , Albertini Richard J. 
Published: February 2007

AbstractIn order to characterize in vivo gene mutations that occur during fetal development, molecular analyses were undertaken of mutant 6‐thiogua‐nine resistant T‐lymphocytes isolated from placental cord blood samples of 13 normal male newborns. These mutant T‐cells were studied to define hypoxanthine‐guanine phosphoribosyl‐transferase (hprt) gene structural alterations and to determine T‐cell receptor (TCR) gene rearrangement patterns. Structural hprt alterations, as shown by Southern blot analyses, occurred in 85% of these mutant clones. These alterations consisted mostly of deletion of exons 2 and 3. These findings contrast with the 10–20% of gross structural alterations (i.e., those visible on Southern blots) occurring randomly across the entire gene previously reported for T‐cell mutants isolated from normal young adults. Iterative analyses of hprt structural alterations and TCR gene rearrangement patterns show that approximately one‐third of the newborn derived mutants may have originated as pre‐ or intrathymic hprt mutations. This too contrasts with previous findings in adults where the background in vivo hprt mutations appeared to originate in post‐thymic T‐lymphocytes.
Effect of interleukin‐2 on cell proliferation, sister‐chromatid exchange induction, and nuclear stress protein phosphorylation in Pha‐stimulated fischer 344 rat spleen lymphocytes: Modulation by 2‐mercaptoethanol
Authors: Morris Suzanne M. , Aidoo Anane , Domon Olen E. , McGarrity Lynda J. , Kodell Ralph L. , Schol Henry M. , Hinson William G. , Pipkin James L. , Casciano Daniel A. 
Published: February 2007

AbstractThe effect of interleukin‐2 (IL‐2) on cell proliferation, sister‐chromatid exchange (SCE) frequency, and the phosphorylation of nuclear stress proteins was evaluated in phytohemagglutinin (PHA)‐stimulated spleen lymphocytes isolated from Fischer 344 rats. In addition, the ability of 2‐mercaptoethanol (2‐ME) to modulate the induction of these biological responses was characterized. Cell proliferation, as measured by the mitotic index, increased significantly (P < .003) from a range of 3‐4% in PHA‐stimulated cultures to a range of 8‐11% in PHA‐stimulated cultures exposed to IL‐2. The average generation time (AGT) did not respond to IL‐2 in a concentration‐dependent manner and decreased significantly (P < .05) when 20 μM 2‐ME was includedwith IL‐2 in the culture medium. The number of SCE increased significantly (P < .004) from control frequencies, which ranged from 13.1 to 15.6 SCE per cell, to frequencies of 18.5 to 21.5 SCE per cell as the concentration of IL‐2 in the culture medium increased to 50 half‐maximal units per ml. A reduction in SCE frequency was observed when cells were cultured with 20 μM 2‐ME and IL‐2 compared to IL‐2 alone. Three nuclear proteins, with relative molecular masses of approximately 13,000‐18,000, 20,000, and 80,000, were phosphorylated in IL‐2‐exposed G1‐phase nuclei. Elicitation of these nuclear proteins in IL‐2‐exposed cells was not affected by exposure to 2‐ME.
Induction of nuclear aberrations by smokeless tobacco in epithelial cells of human oral mucosa
Authors: Livingston Gordon K. , Reed Robert N. , Olson Byron L. , Lockey James E. 
Published: February 2007

AbstractCytologic and cytogenetic studies were performed to assess the prevalence of somatic cell genetic damage in 48 young adults equally divided to represent users and nonusers of smokeless tobacco. Exposure was ascertained by measuring saliva cotinine using capillary gas chromatography. Squamous epithelial cells sampled from the oral mucosa demonstrated significant cytologic alterations associated with tobacco exposure. The frequency of micronucleated cells was significantly (P < .01) higher in the labial mucosa of exposed (2.22%) compared to unexposed (0.27%) individuals. The frequency of micronuclei varied widely between exposed subjects but was higher in heavily (2.48%) compared to lightly (1.29%) exposed individuals as measured by saliva cotinine levels. Morphologic classification of epithelial cell nuclei showed that the frequency of cells with normal nuclear structure was significantly (P < .01) reduced in exposed individuals. Analysis of oral epithelial cells of five additional nonusers of smokeless tobacco but wearers of orthodontic appliances to simulate abrasion demonstrated no difference from the nonexposed control group. Unlike the case with cigarette smokers, peripheral lymphocyte sister‐chromatid exchange frequency was not affected by exposure to smokeless tobacco. The oral cytology data, however, support an interpretation of exposuredependent nuclear alterations, including micronuclei, in the oral epithelium associated with the use of smokeless tobacco. Altogether, results suggest that use of smokeless tobacco, may cause genetic damage to cells in the oral epithelium.
Mutagenesis in Escherichia coli lacking catalase
Authors: Abril Nieves , Pueyo Carmen 
Published: February 2007

AbstractEscherichia coli K‐12 strains completely lacking catalase activity due to mutations in katG, katE, and katF genes were constructed in order to assess the role of hydrogen peroxide in mutagenesis. Mutagenesis was monitored by selecting forward mutations to L‐arabinose resistance. Lethality was measured at experimental conditions equivalent to those of the mutant yield by using a mixed culture of pairs of isogenic strains distinguished by their differential nutritional requirements. Deficiency in katG, katE, and katF genes leads to an enhanced spontaneous mutation rate as well as an enhanced sensitivity to both the lethal and mutagenic effects of hydrogen peroxide or an H2O2‐generating mixture of compounds, such as coffee. To compare further the responses of the catalase‐deficient bacteria to those of catalase‐proficient counterparts, other genotoxins were analyzed. Both catalase‐deficient and catalase‐proficient strains were equally mutated by MMS, 4‐NQO, and ultraviolet light. It is concluded that the bacterial strains and the mutagenicity tests described in the paper represent a useful tool to study the role of H2O2 in mutagenesis.
The simultest approach for testing mutagens in the Salmonella Microtitre fluctuation assay
Authors: McPherson Marcia F. , Nestmann Earle R. , Hartman P. E. 
Published: February 2007

AbstractThe concept of combining several histidine‐dependent Salmonella strains in a single test, the SIMULTEST, has been applied to the microtitre fluctuation test. The activity of five mutagens was determined in strains TA97, TA98, TA100, and TA102 individually as well as in a SIMULTEST mixture. All five compounds were mutagenic in the SIMULTEST, demonstrating the utility of this time and labour‐saving approach of combining strains for testing with this method. The microtitre fluctuation SIMULTEST results were quantitatively comparable to those of the SIMULTEST Salmonella/microsome plate test. The microtitre fluctuation test compared with the plate incorporation assay generally showed more favourable “sensitivity” and “quantity” indices in that four of the five chemicals tested in the fluctuation test were mutagenic at lower doses than in the plate test.
2,[3]terf‐Butyl‐4‐hydroxyanisole does not reduce SCE induction by benzo (a) pyrene in bone marrow cells of C57BL/6 Mice
Authors: Horn Randall Van , Dewire Faith A. , Barnes William S. , Carrano A. V. 
Published: February 2007

AbstractRecently, a number of publications have suggested that bone marrow cytogenetics may be used to detect anticarcinogenic or antimutagenic activity. In this work, 0.75% 2,[3]‐tert‐butyl‐4‐hydroxyanisole (BHA), fed in the diet for 2 weeks, was tested for its ability to reduce the frequency of benzo(a)pyrene (BP)‐induced SCE in mouse bone marrow. C57BL/6 male mice, were injected i.p. with BP at 0, 33, 67, and 100 mg/kg body weight. The mean SCE/chromosome ± s.e.m. for animals on control diet was 0 mg/kg, 0.108 ± 0.005; 33 mg/kg, 0.225 ± 0.011; 67 mg/kg, 0.289 ± 0.012; 100 mg/kg, 0.311 ± 0.013. The mean SCE/chromosome ± s.e.m. for animals on the 0.75% BHA diet was 0 mg/kg, 0.105 ± 0.006; 33 mg/kg, 0.224 ± 0.009; 67 mg/kg, 0.262 ± 0.013; 100 mg/kg, 0.326 ± 0.012. There are no significant differences between animals on the control and BHA diets. Excretion of BP in urine over a 72 hr time period was significantly increased in animals on the BHA diet, at both low and high doses. Water‐soluble metabolites accounted for all of this increase. It appears that bone marrow is not a good model for the gastrointestinal tract, and that short‐term assays for anticarcinogens or antimutagens are more likely to be predictive if they are done in the target organs.
DNA adduct formation in rat alveolar type II cells: Cells potentially at risk for inhaled diesel exhaust
Authors: Bond James A. , Johnson Neil F. , Snipes M. Burt , Mauderly Joe L. , Sega G. A. 
Published: February 2007

AbstractDiesel exhaust (DE) is a pulmonary carcinogen in rats. One potential mechanism for DE‐induced carcinogenicity involves the interaction of the organic chemicals associated with DE soot with DNA in target cells. The purpose of this study was to determine whether peripheral lung cells, specifically alveolar type II cells, are at risk from inhaled DE. Rats were exposed 16 hr/day, 5 days/week to filtered air (controls), carbon black (CB) (6.2 mg/m3), or to diluted DE (6.2 mg/m3) for 12 weeks. CB particles were used for comparison with DE soot, because the CB particles are morphologically similar to soot particles, but are virtually devoid of adsorbed organic compounds. Type II alveolar cells were isolated by flow cytometry and DNA in the cells was analyzed for DNA adducts using the 32P‐postlabeling assay. There was a significant increase (˜ 4‐fold) in the level of total adducts in type II cells of rats exposed to DE and CB, compared with sham‐exposed rats. While exposure to CB and DE induced the formation of adducts that were not consistently seen in sham‐exposed rats, exposure to these materials also appeared to increase the intensity of adducts present in type II cells from sham‐exposed rats. These data underscore the importance of investigating molecular dosimetry at the biological level of the cell. We conclude that the type II alveolar cell may be a risk for damage from inhaled DE.
Comparison of mutagenic activities of several peroxyacyl nitrates
Authors: Kleindienst Tadeusz E. , Shepson Paul B. , Smith David F. , Hudgens Edward E. , Nero Chris M. , Cupitt Larry T. , Bufalini Joseph J. , Claxton Larry D. , Nestman F. R. 
Published: February 2007

AbstractSalmonella typhimurium, strain TA100 was exposed to a series of peroxyacyl nitrates including peroxyacetyl nitrate (PAN), peroxypropionyl nitrate (PPN), peroxybutyryl nitrate (PBN), peroxybenzoyl nitrate (PBzN), and chloroperoxyacetyl nitrate (CPAN). Gas‐phase concentrations for the individual exposures were in the high part per billion by volume ppbv range. The dose was determined from the deposition rate and measured from the net decrease of the test compound in the exposure chamber and the exposure time. The mutagenic activity for each compound determined from the dose‐response relationship gave values ranging from 250 (PBN) to 6,500 (PBzN) revertants/μmol. The mutagenic activity for CPAN could not be determined, due to an interference from chloroacetaldehyde. The difficulties of quantifying the actual gas‐phase chemical dose the bacteria are exposed to in this variant of the Ames test are delineated.