bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical enhancement of survival in aggregation of retrovirus‐infected rat cells: An interlaboratory comparison
Authors: Suk W. A. , Poiley J. A. , Raineri R. , Steuer A. F. , Tennant R. W. 
Published: February 2007

AbstractThis study provides a comparative evaluation among three independent laboratories of the responses to 16 chemicals in the retrovirus (Rauscher leukemia) infected Fischer rat embryo (RIFRE) cell‐survival‐in‐aggregation assay. When suspended in liquid media above an agar base, control cells showed a rapid decline in cell survival, whereas cells that had previously been treated with chemical carcinogen survive in suspension longer than control cells. The endpoint, survival in aggregation, is measured by counting viable cells dissociated from aggregates in suspension for 4 days. By modifying previously reported procedures, we have improved the system so that a clear differential (positive or negative) response is achieved by cells treated with either a known carcinogen or known noncarcinogen. Using procedures designed to minimize assay variability, replicate assays were performed and the data analyzed for inter‐ and intralaboratory concordance. The RIFRE cell‐survival‐in‐aggregation assay demonstrated a high degree of interlaboratory reproducibility in assessing the overall positive or negative responses of known carcinogens and noncarcinogens, and good qualitative reproducibility in assessing compounds tested under code. The assay could discriminate between known carcinogens and noncarcinogens. All chemicals were tested without the addition of a metabolic activation system. Cells exhibiting carcinogen‐induced enhancement of survival in aggregation, when plated back onto a solid substrate and carried in culture, subsequently expressed transformation‐associated changes in their cellular morphology, growth in semisolid media, and tumorigenicity in nude mice. These results indicate that retrovirus‐infected Fischer rat embryo cells detect a carcinogen‐mediated early event that progresses to neoplastic phenotypes. Survival in aggregation appears to require the presence of the exogenous retrovirus, since uninfected cells did not show a differential survival response when carcinogen‐treated, noncarcinogen‐treated, or control cells were compared. This system provides a reproducible method of detecting carcinogenic chemicals based on their ability to induce enhanced survival in aggregation of treated cells.
Mutagenicity of algal metabolites of benzo(a)pyrene for Salmonella typhimurium
Authors: Schoeny Rita , Cody Terence , Radike Martha , Warshawsky David 
Published: February 2007

AbstractThe metabolism and growth effects of benzo(a)pyrene (BaP) were studied using a freshwater green alga, Selenastrum capricomutum. Algal cultures were incubated under gold light with BaP added at concentrations of 40, 160, 400, and 1,200 μ liter for the periods of 1–4 days. The metabolites and BaP were identified and quantified from ethyl acetate extracts of both algal cells and incubation medium. The ethyl acetate extracts were evaluated for genotoxicity using a micro‐volume Salmonella typhimurium forward mutation assay with resistance to 8‐azaguanine for selection. This assay detected the presence of small quantities of BaP and was particularly sensitive to the mutagenicity of BaP diols. Of those extracts prepared from algae and medium from cultures exposed to 400 μ BaP/liter (10 μ/25 ml culture), only algal cell extracts from one day's growth were mutagenic. In cultures exposed to 1,200 μ BaP/liter (30 μ /25 ml culture), mutagenic materials were produced or persisted in both algae and media throughout the 4‐day incubation. The observed mutagenic response can be attributed in part to the presence of unmetabolized BaP or to BaP diols.
Ethylene oxide dose and dose‐rate effects in the mouse dominant‐lethal test
Authors: Generoso W. M. , Cain K. T. , Hughes L. A. , Sega G. A. , Braden P. W. , Gosslee D. G. , Shelby M. D. 
Published: February 2007

AbstractIn the dose‐response study, male mice were exposed by inhalation to ethylene oxide (EtO) for 4 consecutive days. Mice were exposed for 6 hr per day to 300 ppm, 400 ppm, or 500 ppm EtO for a daily total of 1,800, 2,400, or 3,000 ppm hr (total exposures of 7,200, 9,600 and 12,000 ppm hr), respectively. In the dose‐rate study, mice were given a total exposure of 1,800 ppm hr per day, also for 4 consecutive days, delivered either at 300 ppm in 6 hr, 600 ppm in 3 hr, or 1,200 ppm in 1.5 hr. Quantitation of dominant‐lethal responses was made on matings involving sperm exposed as late spermatids and early spermatozoa, the most sensitive stages to EtO. In the dose‐response study, a dose‐related increase in dominant‐lethal mutations was observed, the dose‐response curve proved to be nonlinear. In the dose‐rate study, increasing the exposure concentrations resulted in increased dominant‐lethal responses.
Mutation and enhanced virus transformation of cultured hamster cells by exposure to gaseous ethylene oxide
Authors: Hatch George G. , Conklin Patricia M. , Christensen Carla C. , Anderson Tara M. , Langenbach Robert , Nesnow Stephen 
Published: February 2007

AbstractEthylene oxide is a classical mutagen and a carcinogen based on evidence from studies in experimental animals. It is widely distributed in industrial, research, hospital, and food environments. In an effort to explore the use of newly developed methods for exposing mammalian cells to gaseous or volatile mutagens/carcinogens, Chinese hamster V79 cells were treated for 2 hr with gaseous ethylene oxide, in sealed treatment chambers, and assayed for survival and mutagenic response by analysis of induced resistance to 6‐thioguanine or ouabain. Significant numbers of mutants were produced at both genetic markers by 1,250–7,500 ppm ethylene oxide. Similarly, primary Syrian hamster embryo cells were treated for 2 or 20 hr with gaseous ethylene oxide in sealed treatment chambers and subsequently assayed for survival and increased sensitivity to SA7 virus transformation. Treatment concentrations extended from toxic to several nontoxic concentrations. After 2‐hr ethylene oxide treatment at 625–2,500 ppm a significant enhancement of virus transformation was observed. At 20 hr after treatment no enhancement was observed. Treatment of hamster cells with ethylene oxide in both bioassay systems yielded concentration‐related, quantitative results.
The effect of acrylamide on hepatocellular dna repair
Authors: Miller Mary Jo , McQueen Charlene A. 
Published: February 2007

AbstractAcrylamide has recently been reported to induce tumors in laboratory animals. The effect of acrylamide on unscheduled DNA synthesis using the hepatocyte primary culture (HPC)/DNA repair test was examined. Isolated hepatocytes were exposed to acrylamide and [3H]thymidine ([3H]TdR) for 18 hr. Incorporation of [3H]TdR into DNA was determined by autoradiography. No DNA repair was observed at acrylamide concentrations up to 10‐2 M. These findings were confirmed using density gradients. Acrylamide concentrations exceeding 10‐2 M were cytotoxic to hepatocytes. Because both autoradiography and density gradients measure DNA repair as an endpoint, the ability of acrylamide to inhibit these repair processes was also determined. Acrylamide had no effect on the repair of UV‐damaged DNA. These results show that acrylamide is not genotoxic in isolated hepatocytes.
Bacterial mutagenicity and chemical analysis of polycyclic aromatic hydrocarbons and some nitro derivatives in environmental samples collected in West Germany
Authors: Garner R. C. , Stanton C. A. , Martin C. N. , Chow F. L. , Thomas W. , Hubner D. , Herrmann R. 
Published: February 2007

AbstractSnow and air particulate samples collected in Upper Frankonia, Federal Republic of Germany, have been analyzed for nitro‐polycyclic aromatic hydrocarbons (PAH) and PAH content. A novel clean‐up technique has been developed enabling interfering organochlorine environmental contaminants to be removed prior to analysis of the hydrocarbons by GC‐MS. Mass fragmentation patterns are presented for 1‐nitropyrene, 6‐nitrobenzo(a)pyrene, 6‐nitrochrysene, and 3‐nitrofluoranthene. The level of these compounds found in air samples was in the range of 0.2–2.0 ng·m−3 with the exception of 6‐nitrobenzo(a)pyrene, which was not detected. This compares with PAH values of between 1 and 6 ng.m−3. The freshly fallen snow sample collected at the side of a motorway had no detectable PAHs or nitro‐PAHs. Parallel studies on the bacterial mutagenicity of the collected air samples using Salmonella typhimurium TA98 and TA100 in the presence and absence of aroclor‐induced rat liver “S9” revealed both “direct” and “indirect” activity. Larger numbers of mutants were induced in the presence of S9 than in its absence. The snow sample was devoid of mutagenic activity. These studies show the utility of the biological approach to screen environmental samples prior to expensive and time‐consuming chemical analysis.
A semiselective test for the detection of first‐ and second‐division nondisjunction in Drosophila melanogaster
Authors: Foureman Polly A. 
Published: February 2007

AbstractLittle is known about the relative frequency of induction of nondisjunction in the first and second divisions of meiosis. The Killer of prune system is a semiselective Drosophila aneuploidy assay designed to detect chromosome gain resulting from first‐ or second‐division nondisjunction in males. The system can also detect X‐Y interchange. Extensive data from nonmutagenized controls indicate that all the expected phenotypes can be recovered. Spontaneous nondisjunction in the first division is three times more frequent than in the second division. Spontaneous interchange between the X chromosome and YS is six times more frequent than between the X chromosome and YL. Exposures of larval males to X‐rays, 35°C heat shock, and colchicine were performed. X‐ray exposure induced an increase in X‐Y interchange events only. A 24‐hr heat shock induced an increase in first‐division nondisjunction and one type of interchange event. Colchicine failed to induce both nondisjunction and interchange, although it did decrease fertility. The Killer of prune test is of potential value because it allows for the assessment of the relative sensitivities of the two meiotic divisions to perturbations in chromosome number.
Measurement of in vivo mutant frequency in lymphocytes in the mouse
Authors: Dempsey J. L. , Morley A. A. 
Published: February 2007

AbstractA limiting‐dilution cloning technique for quantifying in vivo mutations at the hypoxanthine phosphoribosyl transferase locus in mouse splenocytes was developed. Mouse splenocytes were cultured in round‐bottom microwells with irradiated feeder cells, concanavalin A, and a source of interleukin 2 at five cells/well in the absence of thioguanine, and at 5 × 104 cells/well in the presence of 2.5 μg/ml thioguanine; mutant frequency was calculated as the ratio of the cloning efficiencies with or without thioguanine. The geometric mean (95% range) for the mutant frequency in 20 mice was 1.54 × 10−6 (4.7 × 10−7‐2.6 × 10−6) and whole‐body X‐irradiation resulted in a dose‐related increase in mutant frequency of up to approximately 20 times the baseline level. The in vivo murine mutation assay should be a useful system for genotoxicity testing and may be of particular value in establishing risk estimates for human populations exposed to genotoxins.
6‐methylmercaptopurine riboside resistance in human lymphocytes in the in vivo somatic cell mutation test
Authors: Wong Y.‐W. , Tomkins D. J. 
Published: February 2007

AbstractAdditional drug‐resistance markers are being investigated to broaden the in vivo somatic cell mutation test in human lymphocytes (PBL). The adenosine kinase (AK) locus was chosen for study because Gupta and Singh [Gupta RS, Singh B: Mutat Res 113:441–454, 1983] have demonstrated that in Chinese hamster ovary cells, mutants affected at this locus are obtained at a very high spontaneous frequency and that the response of this locus to different types of mutagens was comparable to that of the hypoxanthine‐guanine phosphoribosyl transferase locus. The adenosine analog 6‐methylmercaptopurine riboside (MeMPR) was used as the selective agent for obtaining AK‐deficient mutants. Cultures of mitogen‐stimulated PBL were set up in the presence (test) and absence (control) of the selective agent. Resistant cells capable of synthesizing DNA in the presence of MeMPR were labeled with tritiated thymidine and enumerated autoradiographically. The variant frequency (Vf) was calculated as the ratio of the number of labeled nuclei in the test relative to that in the control. Human PBL were found to be sensitive to MeMPR inhibition of DNA synthesis and exhibited a dose‐dependent decrease in Vf with increasing concentrations of MeMPR. However, no leveling off of the dose‐response curve was observed. Thus the background level of Vf was probably lower than the practical detection limit of the test (4.0 × 10−7 with a 50‐ml blood sample). It was concluded that, because of the autosomal recessive nature of the AK gene, the background Vf in human PBL is too low to allow a useful baseline to be established for the in vivo somatic mutation test.
Comparison of S9 mix and hepatocytes as external metabolizing systems in Mammalian cell cultures: Cytogenetic effects of 7,12‐dimethylbenzanthracene and aflatoxin B1
Authors: Madle Elisabeth , Tiedemann Gudrun , Madle Stephan , Ott Angelika , Kaufmann Gabriele 
Published: February 2007

AbstractTwo external metabolizing systems, S9 mix from Aroclor‐induced rat livers and freshly isolated hepatocytes, were used for activation in cultures of human lymphocytes and V79 cells. 7, 12‐dimethylbenzanthracene (DMBA) and aflatoxin B1 (AFB1) were employed as indirectly acting reference mutagens. Mutagenic effects were measured by induction of sister chromatid exchange (SCE). With DMBA, SCE‐inducing effects were found to be quite similar after activation by S9 mix and activation by hepatocytes. In human lymphocytes nearly the same dose‐effect relationships were found with both metabolizing systems; in V79 cells the hepatocyte‐mediated induction of SCE was detectable at slightly lower concentrations than the S9‐mediated SCE induction. In contrast with AFB1, S9 activation led to a stronger SCE induction than hepatocyte activation in both target cells. The induction of chromosomal aberrations by AFB1 after activation by the two metabolizing systems was also analysed in V79 cells. This experiment again revealed that AFB1 was more efficiently activated by S9 mix than by hepatocytes, and it appeared that AFB1 is a more potent inducer of chromosomal aberrations than of SCE. The different activation capacities of the two metabolizing systems for AFB1 may be due to the maintenance of inactivation mechanisms in hepatocytes or to the Aroclor induction of the S9 fraction. Our experiments have shown that the suitability of hepatocytes as an activation system is not restricted to microbial or eukaryotic point mutation assays, but that hepatocyte metabolism can also be successfully included in cytogenetic tests with short‐ and long‐term cultures of mammalian target cells.
A comparison of baseline and cyclophosphamide‐induced sister chromatid exchanges in bone marrow and spleen cells of mouse and chinese hamster
Authors: Krishna G. , Nath J. , Petersen M. , Ong T. 
Published: February 2007

AbstractBaseline sister chromatid exchange (SCE) frequencies were investigated in bone marrow and spleen cells of mice and Chinese hamsters. No significant difference in SCE frequency was noted for bone marrow in both species and for bone marrow and spleen in mice on per cell and per pg DNA basis. However, a significant difference was noted between species in spleen and between cell types in Chinese hamsters. Also, statistically significant differences were noted between species for both cell types when the same data were expressed on per chromosome basis. SCE levels in cultured bone marrow and spleen cells after intraperitoneal administration of the antineoplastic drug cyclophosphamide (10 and 20 mg/kg) differed significantly in mice and Chinese hamsters on per cell, per pg DNA content, and per chromosome basis. The spleen cells were much more sensitive to the effects of cyclophosphamide than bone marrow cells in both species. The replicative indices did not differ significantly between treated and control animals in either bone marrow or spleen cells of both species. Since SCE frequency is a sensitive measure of DNA damage, and bone marrow and lymphocytes are the most widely used cell types in human and animal in vivo assays, the methodologies and results reported here may be useful for comparative mammalian cytogenetic studies.
Chemical enhancement of SA7 virus transformation of hamster embryo cells: Evaluations by interlaboratory testing of diverse chemicals
Authors: Hatch G. G. , Anderson T. M. , Lubet R. A. , Kouri R. E. , Putman D. L. , Cameron J. W. , Nims R. W. , Most B. , Spalding J. W. , Tennant R. W. , Schechtman L. M. 
Published: February 2007

AbstractTwelve chemicals from diverse structural classes were tested under code for their capacity to enhance the transformation of Syrian hamster embryo cells by simian adenovirus SA7 in two independent laboratories. Pretreatment of hamster cells with eight of those chemicals (reserpine, dichlorvos, methapyrilene hydrochloride, benzidine dihydrochloride, diphenylhydantoin, cinnamyl anthranilate, 11‐amino‐undecanoic acid, and 4,4′‐oxydianiline) produced repeatable enhancement of SA7 transformation at two or more consecutive dose levels, which constitutes clear evidence of enhancing activity in this assay. Both toxic and nontoxic doses of each of these chemicals caused enhancement of virus transformation. Two chemicals (2,6‐dichloro‐p‐phenylenediamine and cinnamaldehyde) produced some evidence of enhancing activity (repeatable transformation enhancement at one dose). Dose ranges for cytotoxicity and enhancement of SA7 transformation were similar in both laboratories for all chemicals producing activity. The final two chemicals, chloramphenicol sodium succinate and ethylene thiourea, failed to reproducibly demonstrate either significant cytotoxicity or enhancement of SA7 transformation at concentrations up to 10–20 mM. The test results for these 12 chemicals were combined with the test results for 9 known carcinogens and noncarcinogens in order to evaluate relationships between activity, dose response, and lowest effective enhancing concentration for these compounds, as well as to correlate them with rodent carcinogenesis classifications. The Syrian hamster embryo cell‐SA7 system demonstrated reproducible test responses in both intra‐ and interlaboratory studies and detected 13 out of 15 known rodent carcinogens.
Variation in sister chromatid exchange frequencies between human and pig whole blood, plasma leukocyte, and mononuclear leukocyte cultures
Authors: Larramendy Marcelo L. , Reigosa Miguel A. 
Published: February 2007

AbstractSister chromatid exchange (SCE) induction by ultraviolet (UV) light was studied in both human and pig whole blood cultures (WBC) and plasma leukocyte cultures (PLC). No variation in SCE frequency was observed between pig WBC and PLC in control as well as in treated cells. Conversely, SCE frequencies of human PLC were consistently higher than those of WBC in control and UV‐exposed cells. Thus, red blood cells (RBCs) do not influence the sensitivity of lymphocytes to UVlight exposure, and there must be some different culture condition(s) in the induction of SCEs between human WBC and PLC but not in swine lymphocyte cultures. Since the BrdUrd/lymphocyte ratio of WBC was halved in PLC, the effect of BrdUrd concentration in inducing the SCE baseline frequency of PLC may be ruled out. Also, Ficoll‐Hypaque‐separated human mononuclear leukocytes in culture (MLC), but not pig MLC, showed a two‐fold increase in SCE frequency over WBC values. Thus, neither the cell separation technique nor polymorphonu‐clear leukocytes had a significant role in the elevated SCE frequency of human PLC or MLC. Experiments where human RBCs were titrated into human PLC showed that the induction of an elevated SCE frequency of PLC was suppressed in a dose‐dependent manner by the presence of RBCs in the culture medium. Since the incorporation of pig or human RBCs into human PLC as well as into MLC reduced the SCE frequency to that of WBC, a common component and/or function existing in these cells is suggested. Analysis of different RBC components showed that RBCs, specifically RBC ghosts, release a diffusible but not dialyzable “corrective” factor into culture medium that is able to reduce the SCE frequencies of PLC. Antioxidant enzymes such as catalase and horseradish peroxidase were unable to reduce the SCE frequency of human PLC to WBC values.
NPPD (Spy dust) is predicted to be a mutagen
Authors: Klopman Gilles , Kalos Alex , Frierson Manton , Rosenkranz Herbert S. 
Published: February 2007

AbstractWith the aid of CASE, the Computer Automated Structure Evaluation system, a new artificial intelligence procedure to study structure‐activity relationships and a data base consisting of 233 monocyclic nitroarenes, it is predicted that 5‐(4‐nitrophenyl)‐2,4‐pentadienal will be mutagenic for Salmonella typhimurium but that the activity will be very low.
Patterns of mutagen binding and penetration in multicell spheroids
Authors: Olive Peggy L. 
Published: February 2007

AbstractMutagen damage to a cell located at some distance from the site of application of the mutagen will depend, in part, on how effectively it can penetrate through cells composing different tissues. Chinese hamster V79 spheroids were used to model mutagen “penetrability” by providing several layers of cells growing with tissue‐like packing. By treating cells of intact and trypsin‐dissociated spheroids at the same drug‐to‐cell ratio, an estimate relative sensitivity to nine mutagens was determined. The effective toxicity index (ETI) was defined as the ratio of the concentrations of mutagen required to kill 50% of cells (measured after a 1‐hr treatment at 37°C) in dissociated versus intact spheroids and similarly for mutation at the HGPRT locus (EMI). Values for ETI were consistent with values for EMI and varied from 0.01 for 4NQO to 2 for AF‐2. Direct information on mutagen penetration was obtained for fluorescent mutagens by flow cytometry. Values for EFI (effective fluorescence index) varied from 0.07 for Hoechst 33342 to 1 for AF‐2. These results can be interpreted as reflecting differences in ability of mutagens to penetrate spheroids; some direct‐acting mutagens are likely to be effective only near their site of application (ie, UV, Hoechst 33342, 4NQO) while others are able to penetrate through successive cell layers with little difficulty (ie, monobromobimane, AF‐2).
Chromium (VI) comutagenesis: Characterization of the interaction of K2CrO4 with azide
Authors: Lavelle James M. 
Published: February 2007

AbstractIn a previous report chromate potentiated the mutagenicity of sodium azide, apparently by affecting repair and/or replication of DNA. Further evidence in support of such a mechanism for chromate potentiation is reported here. Chromate does not react directly with azide or its major mutagenic metabolite, azidoalanine, eliminating such reactions as possible mechanisms for potentiation. Further, azide was unable to potentiate the mutagenicity of chromate in Salmonella typhimurium strain TA104, which is sensitive to chromate mutagenicity but not to azide. Thus, it appears that the potentiation is not due to an action of azide in modulating chromate mutagenicity. Finally, the interaction was not altered by deficiency in recA gene product in S typhimurium GW19, nor by enhancement of SOS repair in the pKM101 containing strain TA100. Thus, induction of recA‐dependent functions seems to play no role in the comutagenic actions of chromate. The simplest explanation for potentiation seems to be that chromate is able either to limit error‐free recovery from azide‐induced DNA damage or to promote error‐prone repair or error‐prone processing at sites of lesions.