bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sister chromatid exchange studies in human fibroblast—rat hepatocyte co‐cultures: A new in vitro system to study sces
Authors: Kligerman Andrew D. , Strom Stephen C. , Michalopoulos George 
Published: February 2007

AbstractTo approximate better the metabolic reactions that take place in vivo yet maintain the simplicity and reproducibility of in vitro systems, we have developed a co‐culture system making use of freshly isolated rat hepatocytes and confluent human fibroblasts for the study of SCE induction by genotoxic agents. Hepatocytes were obtained from male rats by reverse collagenase perfusion and plated over low‐passage male human fibroblasts. Preliminary studies demonstrated that although the number of hepatocytes plated was not critical, the best attachment to, and coverage of, the fibroblasts occurred when between 10 × 106 and 20 × 106 hepatocytes were plated/100 mm tissue culture dish. Results with the promutagen cyciophosphamide showed that the hepatocytes could metabolize the compound and deliver active moieties to the fibroblasts resulting in a linear dose‐dependent increase in SCE frequencies. Control fibroblast cultures lacking hepatocytes displayed no increase in SCE frequencies following cyclophosphamide administration.
Hyperthermia induced dissociation of the X‐Y bivalent in mice
Authors: Garriott M. L. , Chrisman C. L. 
Published: February 2007

AbstractThe mutagenic potential of hyperthermia was examined employing a spermatocyte test on males heat stressed continuously for 2, 3, or 5 days. Stress conditions were 35 ± 1° C and 65 ± 3% relative humidity. Males were sacrificed and meiotic preparations made from the testes at various intervals following removal from the stress environment. In this way, chromosome damage could be monitored in all premeiotic and early prophase I stages of spermatogenesis. Results of this study revealed a significant increase in the incidence of X and Y univalents at metaphase I. The significance of this finding is discussed.
Genotoxic activity in microorganisms of tetryl, 1,3‐dinitrobenzene and 1,3,5‐trinitrobenzene
Authors: McGregor Douglas B. , Riach Colin G. , Hastwell Rowan M. , Dacre Jack C. 
Published: February 2007

AbstractN‐Methyl‐N,2,4,6‐tetranitroaniline (tetryl), 1,3‐dinitrobenzene, and 1,3,5‐trinitrobenzene were subjected to DNA repair assays using the Escherichia coli W3110/polA+, p3478/polA− system, reverse mutation assays with His− Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100, and mitotic recombinogenic tests with the yeast Saccharomyces cerevisiae D5. Tests were carried out in the absence of an exogenous activation system and in tissue homogenate‐mediated assays using Aroclor 1254‐induced, male rat‐liver‐derived S9 mix.Mutagenic activity of tetryl was demonstrated with S typhimurium strains TA1537, TA1538, TA98, and TA100. The responses were particularly strong in the absence of S9 mix. Tetryl also induced increases in recombinant numbers and frequencies in the S cerevisiae test without the S9 mix, but not in its presence.1,3‐Dinitrobenzene was demonstrated to be a mutagen with S typhimurium strains TA1538, TA98, and TA100. Slight activity was also seen with TA1537. The S9 mix reduced the magnitude of the responses.1,3,5‐Trinitrobenzene was also demonstrated to be mutagenic with S typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100. Again, the S9 mix reduced the magnitude of the responses.In this segment of a programme initiated by military authorities, the genotoxic potential of three nitroaromatic compounds, which have found significant use in explosive preparations, has been demonstrated.Twelve other compounds used in ordnance were not active in any of the test systems. These were octahydro‐1‐acetyl‐3,5,7‐trinitro‐S‐tetramine (SEX), hexahydro‐1,3‐dinitro‐5‐acetyl‐S‐triamine (TAX), ethyl centralite, 2‐nitrodiphenylamine, N‐nitrosodiphenylamine, diphenylamine, diethyleneglycoldinitrate, nitroguanidine, lead salicylate, lead resorcylate, red phosphorus, and zinc chloride.
The mutagenicity of dialkylaminoalkyl chlorides in a battery of short‐term assays
Authors: Thompson Christina Z. , Rinzel Sharon M. , Probst Gregory S. , McMahon Robert E. 
Published: February 2007

AbstractDialkylaminoalkyl chlorides, valuable chemical manufacturing intermediates, were evaluated for their mutagenicity in several short‐term assays: The concentration gradient bacterial mutagen assay, the Ames test, the L5178Y mouse lymphoma cell assay, and the hepatocyte primary culture‐DNA repair test. The dialkylaminoethyl chlorides were active in all test systems. The relative mutagenic potencies of the ethyl chlorides were similar in the bacterial tests and the L5178Y cell assay. The dialkylaminopropyl chlorides were weakly mutagenic in two Salmonella strains but were inactive in the other test systems.The purpose of the test battery used in these studies is to generate data on a test compound which could be used to make a rational prediction of the carcinogenic potential of the compound in test animals. On this basis, the results with the dialkylaminoethyl compounds suggest that if these agents which can form the aziridinium ion were evaluated in in vivo tests there is a reasonable chance some would be found to be carcinogenic. Alternatively, the data on the dialkylaminopropyl chlorides indicate that they have a rather low carcinogenic potential.
Isolation and partial characterization of mutagen‐sensitive and DNA repair mutants of chinese hamster fibroblasts
Authors: Schultz Roger Alan , Trosko James E. , Chang Chia‐Cheng 
Published: February 2007

AbstractThrough a new approach, we have sought to isolate ultraviolet light (UV)‐sensitive and DNA repair mutant Chinese hamster fibroblasts. The procedure consisted of 1) mutation induction by 5‐bromodeoxyuridine (BrdU)‐blacklight and UV treatments; 2) incorporation of 3H‐thymidine in repair‐proficient cells at high temperature (38.5°C) following UV damage; 3) cold holding (4.0°C) of these cells to induce tritium killing; and 4) recovery and testing of repair‐deficient and UV‐sensitive cells which have survived and formed colonies at low temperature (34.0°C). In our initial attempt at this protocol, we isolated 72 surviving colonies from 2 × 107 cells plated for selection. Of the 72 colonies. 20 demonstrated potential interest and four were selected for extensive study. One, identified as UVs−7, is slightly more sensitive to UV, but not sensitive to X rays or N‐acetoxy‐2‐acetylaminofluorene (NAc‐AAF). The mutant exhibits a highly reduced level of unscheduled DNA synthesis (UDS), as compared to the parental line. Two additional lines, UVs−40 and UVs−44, are sensitive to UV, X ray, N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG), and NAc‐AAF, but exhibit normal UDS. A fourth line, UVr−23, has enhanced UDS, is resistant to UV, but exhibits no difference in sensitivity to X ray or NAc‐AAF. These mutants are all stable, and should be useful for the study of mammalian DNA repair processes and mechanisms of mutagenesis.
The mutation studies of mutagen‐sensitive and dna repair mutants of chinese hamster fibroblasts
Authors: Schultz Roger Alan , Chang Chia‐Cheng , Trosko James E. 
Published: February 2007

AbstractWe have previously reported the isolation and partial characterization of DNA repair and/or mutagen‐sensitive mutant Chinese hamster cell strains. Here we present the results of a detailed study of the ultraviolet light (UV)‐induced mutability of one of these strains, UVs−7, and provide preliminary mutability data on two additional lines, UVr−23 and UVs−40. UVs−7 is extremely deficient in unscheduled DNA synthesis (UDS) but only slightly more sensitive to UV than the parental line. When examined for the UV‐inducibility of mutants resistant to ouabain, 6‐thioguanine, or diphtheria toxin, UVs−7 was found to be hyper‐mutable at all three loci as compared to the parental line. The degree of hypermutability was not the same for any two loci. UVs−40, a highly UV‐sensitive strain, was also found to be hypermutable at the ouabain‐resistant (ouar) locus. UVr−23, which is UV‐resistant and more proficient at UDS than the parental line, appeared to exhibit a tendency toward hypomutability at both the ouabain(ouar) and 6‐thioguanine‐resistant (6TGr) loci. Further characterization of all these lines should aid in delineating mammalian mechanisms of DNA repair and mutagenesis.
Synergistic, additive, and antagonistic mutagenic responses to binary mixtures of benzo(a)pyrene and benzo(e)pyrene as detected by strains TA98 and TA100 in the salmonella/microsome assay
Authors: Hass Bruce S. , Brooks Emily E. , Schumann Karen E. , Dornfeld Suzanne S. 
Published: February 2007

AbstractBinary mixtures of benzo(a)pyrene (B(a)P) and benzo(e)pyrene (B(e)P) produce synergistic mutagenic (comutagenic) responses in Salmonella typhimurium strain TA98 (a frameshift detector). The optimum enhancement (25 ×) was found at B(a)P concentration of 0.3 μg/plate and B(e)P concentration of 1.5 μg/plate. The response of strain TA100 (mostly a base‐substitution detector) is opposite that of TA98, showing antagonism and additivity in similar concentration ranges.
A rapid and simple scheme for confirmation of salmonella tester strain phenotype
Authors: Zeiger Errol , Pagano Dennis A. , Robertson Iain G. C. 
Published: February 2007

AbstractA simple scheme has been developed for confirming the phenotype of the standard set of Salmonella typhimurium tester strains. This scheme employs a series of filter paper discs impregnated with diagnostic mutagens or bacterial toxins. Up to 6 diagnostic discs can be placed on a petri dish to test a single Salmonella strain. The Salmonellae are distinguished by their responses to ampicillin, crystal violet, nitrofurantoin, 9‐aminoacridine, 4‐nitro‐o‐phenylenediamine and sodium azide.
Cytogenetic effects of cis‐platinum(II)diamminedichloride in vivo
Authors: Morrison William D. , Huff Vicki , Colyer Shirley P. , Dufrain Russell J. , Littlefield L. Gayle 
Published: February 2007

AbstractThe chemotherapeutic agent cis‐platinum(II)diamminedichloride (cis‐PDD) has been shown to be mutagenic, teratogenic, and carcinogenic. We determined the cytogenetic effects of cis‐PDD on human and rabbit lymphocytes in vitro and on rabbit marrow cells, lymph node cells, and lymphocytes in vivo. Lymphocyte cultures from two humans and one rabbit were treated in vitro with cis‐PDD. For in vivo studies, five New Zealand white rabbits were given iv injections of cis‐PDD. Posttreatment blood samples were withdrawn for analysis and rabbits were sacrificed at either 6 or 24 hr for cytogenetic analysis of marrow and node cells. Sister chromatid exchange (SCE) analysis of human and rabbit metaphases from lymphocytes treated in vitro showed that rabbit lymphocytes are more sensitive to SCE induction by cis‐PDD. Significant increases in SCE were observed in lymphocyte cultures obtained as early as 1 hr post treatment from injected rabbits. Analysis of node, marrow, and lymphocyte metaphases from injected rabbits showed a high number of chromosome aberrations in these cells with bone marrow showing a delayed response to treatment. These results indicate that cis‐PDD is clastogenic in hematopoietic tissues in vivo and that SCE methodology may be useful in monitoring patients receiving cis‐PDD therapy.
Aneuploidy patterns in drosophila melanogaster
Authors: Traut H. 
Published: February 2007

AbstractBy using an appropriate scheme, various combinations of losses and gains of chromosomes I and II arising in oocytes of Drosophila melanogaster were obtained. The frequencies of these combinations can be arranged as special sequences or patterns which we call “aneuploidy patterns.” Aneuploidy patterns were established for spontaneous, colchicine‐induced, and X‐ray=induced exceptions and were shown to be highly specific for the agent tested. Such patterns can be obtained very quickly, because only exceptional progeny survive. By establishing aneuploidy patterns for chemical agents one would get information on the “aneuploidizing” action of the compounds tested.
Diethylstilbestrol‐diphosphate induces chromosomal aberrations but not sister chromatid exchanges in murine bone marrow cells in vivo
Authors: Ivett J. L. , Tice R. R. 
Published: February 2007

AbstractDiethylstilbestrol diphosphate (DES‐dp) clastogenesis was examined in the bone marrow of C57B1/6 male and female mice. Significant and sex‐related dose effects were observed for the induction of chromatid‐type chromosomal aberrations and for the inhibition of cellular proliferation. Females were more sensitive to the effects of DES‐dp than males when assessed for either induced chromosomal aberrations or proliferative inhibition. Contrary to other published results, we did not observe either an increase in sister chromatid exchanges or an increased incidence of aneuploidy. Ovariectomy reduced the ability of DES‐dp to inhibit cellular proliferation and decreased the high degree of variability between animals at high doses of DES‐dp. The results of our studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.
Herpes virus inactivation by chemical carcinogens: Differential inactivation of herpes simplex viruses by 4‐nitroquinoline 1‐oxide and related compounds
Authors: Speelman Dan , Li Jui‐Lien H. , Ramanujam V.‐M. Sadagopa , Legator Marvin S. , Albrecht Thomas 
Published: February 2007

AbstractTreatment of stocks of herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) with the chemical carcinogen 4‐nitroquinoline 1‐oxide (NQO) resulted in inactivation of virus infectivity at rates which were directly dependent on the concentration of NQO and interval of exposure to NQO. HSV‐1 strains were more sensitive than HSV‐2 strains to inactivation by NQO, although survival curves of both HSV types were multicomponent. Exposure of HSV‐2 to a related group of chemicals suggested that the structural specificity required for inactivation of this virus was similar to that established by previous in vivo carcinogenicity tests.
Effects of acute and chronic administration of mitomycin C on the induction of sister chromatid exchanges in vivo
Authors: Kram David , Bynum Gaither D. , Dean Roger , Schneider Edward L. , Farland William H. , Williams Jerry R. 
Published: February 2007

AbstractFrequencies of sister chromatid exchanges (SCE) were analyzed in bone marrow cells of mice injected with mitomycin C (MMC) both before and during infusion with bromodeoxyuridine (BrdU). Administration of MMC at 1, 6.5, and 13 hours after the onset of BrdU infusion resulted in the induction of approximately 45 SCE/cell, independent of time of administration. When MMC was injected 26 hours prior to BrdU infusion, only baseline levels of SCE were noted. The effects of multiple doses of MMC (chronic administration) were examined in mice treated with 1–5 mg/kg on a weekly or bimonthly basis. SCE analysis was performed one week after the final injection. At all doses and with all treatment regimes, SCE frequencies did not differ from control levels. The results indicate that most or all MMC‐induced DNA damage that results in SCE formation is removed in a single cell cycle after its administration.
Induction by inorganic metal salts of sister chromatid exchanges and chromosome aberrations in human and syrian hamster cell strains
Authors: Larramendy Marcelo L. , Popescu Nicholas C. , Dipaolo Joseph A. 
Published: February 2007

AbstractSister chromatid exchange (SCE) and chromosome aberration induction were determined for several inorganic metal salts. Arsenic, nickel, and beryllium salts at concentrations effective in causing transformation of Syrian hamster cells (HEC) induced SCE and chromosome aberrations of HEC and human lymphocytes, whereas sodium tungstate, a non‐transforming chemical, neither induced SCE nor chromosome aberrations. Normal human and hamster cells exhibited equal sensitivity to SCE induction; nontoxic concentrations of sodium arsenite, beryllium sulfate, and nickel sulfate caused an increase of 8–10 SCE/cell over control values. Sodium arsenite, a trivalent arsenic, and sodium arsenate, a pentavalent arsenic, produced increases in SCE but the former was effective at lower concentrations. Both arsenic salts were less efficient in inducing SCE in human whole blood than in purified lymphocyte cultures. Sodium arsenite, sodium arsenate, nickel sulfate, and beryllium sulfate also caused damage consisting primarily of chromatid type of aberrations. In HEC, with doses most effective in SCE induction, all four metals produced aberrations in 16–21% of cells. In human lymphocytes, 34 and 30% of the cells had chromosome damage after sodium arsenite and sodium arsenate, respectively, whereas beryllium sulfate or nickel sulfate caused damage in about 10% of the cells. The induction of SCE and chromosomal aberrations by metals reemphasizes the sensitivity of cytological assays and their importance for detecting genetic damage caused by carcinogens.
A microsuspension adaptation of the bacillus subtilis “rec” assay
Authors: McCarroll N. E. , Keech B. H. , Piper C. E. 
Published: February 2007

AbstractWe have demonstrated the utility of an Escherichia coli microsuspension assay to detect and characterize chemical mediation of DNA damage by a wide variety of mutagens and carcinogens. The assay has been improved by the development of a microsuspension modification to the Bacillus subtilis “rec” assay. The addition of these gram‐positive organisms has allowed detection of DNA damage induced by benzo[a]pyrene (B[a]P), 3‐aminopyrene (3‐AP), 7, 12‐dimethylbenz[a]anthracene (DMBA), 3‐methylcholanthrene (3‐MC), and 4‐nitrobiphenyl (4‐NBP). Data presented in this paper from tests of 61 additional compounds, including a representative number of direct and promutagenic agents, indicate that the B subtilis H17 and M45 strains provide an effective microbial system for identification of DNA damage susceptible to postreplicational repair. The results of this study further suggests that the inclusion of these strains in the microsuspension assay for DNA damage will markedly enhance the detection of agents which cannot readily penetrate the intact cell wall of E coli.
Mutagenicity of airborne particles from a nonindustrial town
Authors: Whong Wen‐Zong , Stewart John , McCawley Michael , Major Pervis , Merchant James A. , Ong Tong‐Man 
Published: February 2007

AbstractThe mutagenic activity of ambient air particles from Morgantown, West Virginia, has been monitored for 6 months using the Ames Salmonella assay system. Airborne particles, collected on glass fiber filters using a Hi‐Vol sampler, were extracted with dichloromethane (DCM) and/or ethyl acetate plus methanol (E + M) in sequence. A dose‐dependent mutagenic response was observed in Salmonella typhimurium TA 98 for DCM extracts from all samples. E + M extracts were mutagenic only when samples were extracted with E + M before DCM extraction. The mutagenic activity of samples collected in June and July was independent of S‐9 in vitro activation, whereas the mutagenicity of those collected from October to December increased in the presence of S‐9 activation. The class fractionation of extracts showed that only acidic and polynuclear aromatic fractions were mutagenic. The mutagenicity of particles from Morgantown air was also detected with the Salmonella arabinose‐resistant assay system.
Synthesis, chemical characterization, and mutagenic activities of promutagens produced by pyrolysis of proteinaceous substances
Authors: Peters John H. , Mortelmans Kristien E. , Reist Elmer J. , Sigman Caroline C. , Spanggord Ronald J. , Thomas David W. 
Published: February 2007

AbstractChemical and mutagenic characteristics of TRP‐P‐1, TRP‐P‐2, GLU‐P‐1, GLU‐P‐2, GLOB‐P‐1, and GLOB‐P‐2 were evaluated. We synthesized TRP‐P‐1 and TRP‐P‐2 and also obtained samples of these compounds from a commercial source. By GC‐MS analysis, the samples of TRP‐P‐2, GLUs, and GLOBs were more than 99% pure; but the samples of TRP‐P‐1 contained 11–17% of different impurities. These impurities had no effect on the mutagenicity of these chemicals in the Ames test using either strain TA98 or TA100 of Salmonella typhimurium. All six compounds were inactive without metabolic activation and the γ‐carbolines (TRPs) were more active in both strains than the α‐carbolines (GLOBs). GLU‐P‐1 was the most active of the promutagens tested in both TA98 (41,000 revertants/μg) and TA100 (6,580 revertants (μg). In TA98 the order of activity was GLU‐P‐1 > TRP‐P‐2 > TRP‐P‐1 > GLU‐P‐2 ≅ GLOB‐P‐2 > GLOB‐P‐1. In TA100 the order of activity was GLU‐P‐1 ≫ GLU‐P‐2 > TRP‐P‐2 ≅ TRP‐P‐1 ≫ GLOB‐P‐1 ≅ GLOB‐P‐2. We determined the UV absorption and fluorescence characteristics of these compounds, and of HM and NHM, and established an HPLC procedure for their resolution. Sensitivities in the picogram range were attainable using fluorescence detection.
Induction of sister chromatid exchanges and bacterial revertants by organic extracts of airborne particles
Authors: Lockard J. M. , Viau C. J. , Lee‐Stephens C. , Caldwell J. C. , Wojciechowski J. P. , Enoch H. G. , Sabharwal P. S. 
Published: February 2007

AbstractThe genotoxicities of organic extracts of airborne particles have been studied extensively in the Salmonella/mammalian microsome (Ames) test, but in few other bioassays. In these studies, we tested benzene‐acetone extracts of particulate pollutants collected in Lexington, Kentucky, for capacity to induce increases in sister chromatid exchanges (SCE) in human lymphocytes and V79 cells, as well as in the Ames assay. Extracts induced linear dose‐related increases in SCE in human lymphocytes and in bacterial revertants. However, variable responses were observed in SCE assays in V79 cells with and without activation by rat liver S9 or feeder layers of irradiated Syrian hamster fetal cells. We conclude that the SCE assay in human lymphocytes may be a useful indicator of the potential risks to humans of airborne particulate pollutants, as it utilizes human cells recently taken from the host, is rapid and economical, and requires small quantities of test materials. However, thorough studies of the quantitative relationships between SCE induction and mutagenicity in human cells are needed.
Cytotoxicity and mutagenicity of dimethylnitrosamine in mammalian cells (CHO/HGPRT system): Enhancement by calcium phosphate
Authors: O'Neill J. Patrick , Machanoff Richard , San Sebastian Juan R. , Hsie Abraham W. 
Published: February 2007

AbstractThe cytotoxicity and mutagenicity of dimethylnitrosamine (DMN) was determined in the CHO/HGPRT system. Metabolic activation of the promutagen was achieved by use of a liver homogenate supernatant (S9) prepared from Aroclor 1254‐induced Sprague‐Dawley rats. The cytotoxic and mutagenic effects of DMN were enhanced by the inclusion of calcium chloride in the incubation mix, and this enhancement was dependent on the presence of sodium phosphate. Under conditions that yielded maximal activity (10 mM calcium chloride, 10 mM magnesium chloride, 50 mM sodium phosphate), an apparent calcium phospate precipitate was observed. DMN activity increased with increasing amounts of S9 protein over the range 0.3–3.0 mg/ml in the S9 mix and appeared to plateau at higher concentrations. The mutagenicity of DMN can be described as 110 mutants/106 cells per mM DMN per mg/ml S9 protein per hour.