bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors underlying variation in spontaneous and clastogen‐induced sister chromatid exchanges and chromosome breakage frequencies
Authors: Wasserman S. S. , Cohen M. M. , Schwartz S. , Margolin B. H. 
Published: February 2007

AbstractThe latent “factors” influencing spontaneous and clastogen‐induced genetic damage, measured by rates of sister chromatid exchange (SCE) and chromosome breakage (CB), were investigated in a small sample of 20 unrelated, healthy individuals. The covariation of spontaneous and clastogen‐induced (bleomycin [BLM], streptonigrin [SN], mitomycin‐C [MMC], 4‐nitroquinolinel‐oxide [4NQO]) SCEs and CBs was analyzed by maximum‐likelihood factor analysis. A single‐factor model resulted in large standardized regression coefficients of measured variables on the factor for spontaneous and BLM‐ and SN‐induced SCE frequencies, and a modest regression coefficient for MMC‐induced SCEs. A two‐factor model, after varimax rotation, yielded one factor strongly associated with spontaneous and BLM‐ and SN‐induced SCE frequencies, and a second factor associated with spontaneous and BLM‐ and SN‐induced CBs. A bootstrap analysis of this data set indicated the statistical significance of one regression coefficient (i.e., P ≤ 0.05) and borderline significance (0.07 ≤ P ≤ 0.11) of three other regression coefficients on the first factor, to be interpreted as an effector of SCE frequencies. However, for the second factor, none of the bootstrapped regression coefficients was significant (P ≤ 0.22). Due to the modest sample utilized in this study, the validity of this model should be further explored using additional, larger data sets.
salmonella typhimurium (ta100) mutagenicity of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5h)‐furanone and its open‐ and closed‐ring analogs
Authors: Lalonde Robert T. , Cook Gary P. , Perakyla Hannu , Dence Carlton W. , Babish John G. , Carver J. H. 
Published: February 2007

AbstractThe mutagenicities of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX, compound 1), 3‐chloro‐4‐(dichloromethyl)‐2(5H)‐furanone (RMX, compound 6), and 2‐(dichloromethyl)‐3,3‐dichloropropenal (TCB, compound 7) were determined in the same assay and in repetitive determinations using Salmonella typhimurium (TA 100) without microsomal fraction activation. In addition, the mutagenicity of 2‐methyl‐3,3‐dichloropropenal (compound 8) was assayed in the same manner although not simultaneously with MX, RMX, and TCB. This study was undertaken to ascertain the role of open‐ and closed‐ring forms of MX in the mutagenicity of MX. MX proved to be roughly 100 times more mutagenic than the open‐ring analogue TCB and 10 times more mutagenic than the closed‐ring analogue RMX. Compound 8 was inactive. Assay stability of the three active compounds in Vogel‐Bonner medium at 38°C was estimated as the chemical half‐life values by following the change in UV absorbance at selected wave lengths. Half‐life values were 10.7, 2.6, and 2.8 hr, respectively, for MX, RMX, and TCB. The enhanced mutagenicity of MX relative to RMX and TCB is attributed to the intrinsic mutagenicity of MX and its greater stability is judged to play only a minor role. Moreover, the greater mutagenicity of the closed‐ring analogue RMX relative to the open‐ring analogue TCB points to the ring form of MX as the active species even though the open form of MX is predominant under assay conditions.
Reproductive integrity of mammalian cells exposed to power frequency electromagnetic fields
Authors: Livingston Gordon K. , Witt Kristine L. , Gandhi Om P. , Chatterjee Indira , Roti Joseph L. Roti , Littlefield L. G. 
Published: February 2007

AbstractHuman lymphocytes and Chinese hamster ovary (CHO) fibroblasts were analyzed for cytogenetic and cytotoxic endpoints to determine whether exposure to power frequency (60 Hz) electromagnetic fields (EMF) interferes with normal cell growth and reproduction. An exposure chamber was built to apply variable electric current densities of 3, 30, 300, and 3,000 μA/cm2, simultaneously with a fixed magnetic field of 2.2 G to proliferating cells. The current densities were chosen to bracket those that may be induced in the human body by fields measured beneath high voltage (765 kV) power transmission lines. The electric current was applied through the media of a cell culture chamber positioned between two stainless steel electrodes but separated from direct contact with the culture media by a salt bridge composed of a 1% agarose gel. The magnetic field was generated using two pairs of Helmholtz coils driven 73° out of phase producing an elliptically polarized magnetic field 36° out of phase with the electric field. The EMFs were measured and mapped inside the cell culture chamber to insure their uniformity. CHO cells were exposed continuously for 24–96 hr (depending on experiment) and human lymphocytes were exposed continuously for 72 hr. The EMFs were monitored throughout the entire treatment period using a multichannel chart recorder to verify continuous application of the desired fields. Sister‐chromatid exchange and micronuclei were monitored to evaluate the potential for genotoxicity. In addition, standard growth curves, clonogenicity, and cell cycle kinetics were analyzed to evaluate possible cytotoxic effects. The experimental data consistently showed that the growth rate and reproductive integrity of both cell types was unaffected by exposure to the electromagnetic fields.
Aerial oxidation of hydrazines to nitrosamines
Authors: Lunn George , Sansone Eric D. , Andrews A. W. , Zeiger E. 
Published: February 2007

AbstractWhen 1,1‐dimethylhydrazine and N‐aminopiperidine were deliberately exposed to air substantial amounts of the corresponding carcinogenic nitrosamines were formed. Unoxidized samples of 1,1‐dimethylhydrazine were not mutagenic while oxidized samples (which contained much higher levels of nitrosamines) were mutagenic. Both unoxidized and oxidized samples of N‐aminopiperidine were mutagenic.
DNA damage and repair induced by bleomycin in mammalian and insect cells
Authors: Bianchi Néstor O. , M. López‐Larraza Daniel , Dellarco V. L. 
Published: February 2007

AbstractWe assessed the response of mosquito (ATC‐15) and mammalian (CHO) cells to bleomycin (BLM). Comparison of the data obtained in both cell lines indicates that DNA in the chromatin of mosquito cells is 10 to 20 times more resistant to BLM, and that the DNA damage induced by this antibiotic is better repaired in mosquito than in mammalian cells. Permeability of the cell membrane for BLM was found to be the same for both cell lines. Moreover, the time‐kinetics of BLM damage to nuclear DNA was similar for ATC‐15 and CHO cells. The low sensitivity of mosquito cells to BLM is reflected in better growth efficiency. These cells exhibit a satisfactory growth at BLM doses that produce a permanent arrest of growth in CHO cells. It is proposed that variations in the chromatin structure and in the intracellular free amino acid pool may play an important role in the differential response of insect and mammalian cells to BLM.
Increased frequency of chromosomal damage in peripheral blood lymphocytes up to nine years following curative chemotherapy of patients with testicular carcinoma
Authors: Osanto Susanne , Thijssen Joyphi C. P. , Woldering Viola M. , Van Rijn Jaap L. S. , Natarajan Adayapalam T. , Tates Ad D. , Carrano A. V. 
Published: February 2007

AbstractThe presence of micronuclei (MN) in binucleated peripheral blood lymphocytes of 37 testicular carcinoma patients was studied 1.5 to 9.3 years following curative chemotherapy. All patients received cisplatinum, 35 patients also received bleomycin. In addition, most patients were treated with another cytotoxic drug, i.e., vinblastine (n = 23) and/or etoposide (n = 24). The mean time interval between cessation of chemotherapy and the micronucleus assay was 4.6 years. The median frequency of MN in binucleated cells in treated patients (0.059) was significantly higher than that in 12 untreated cancer patients (0.036; P = 0.003) or that in 26 healthy age‐matched controls (0.034; P < 0.001). Frequencies of MN in the 12 untreated cancer patients (including 7 patients with disseminated testicular carcinoma) did not differ from those in the 26 healthy controls (P = 0.890), suggesting that chromosomal damage in lymphocytes of treated testicular cancer patients must be attributed to the chemotherapy. Results indicate that lymphocytes containing chemically induced chromosomal damage persist for up to 9.3 years following cessation of chemotherapy. The implications of these findings with regard to the increased risk for secondary tumors are discussed.
Expulsion of demecolcine‐induced micronuclei from mouse bone marrow polychromatic erythrocytes
Authors: Parton Joseph W. , Garriott Michael L. , Beyers Joe E. , MacGregor J. T. 
Published: February 2007

AbstractThe mouse micronucleus test is a valuable tool for evaluating in vivo chromosome damage produced by test articles in polychromatic erythrocytes of bone marrow. Compounds that are clastogens, such as cyclophosphamide, induce micronuclei that are smaller than those induced by compounds that are spindle poisons, such as demecolcine. In vitro studies have previously shown that the frequency of mitomycin C‐ and vincristine‐induced micronuclei in mouse L‐929 cells was reduced due to micronuclear extrusion following treatment with cytochalasin B. The current study shows that micronuclei are also expelled in vivo, that expulsion is dependent upon micronuclear size, and that observation of these extruded micronuclei is dependent upon the method of sample preparation.
Responses of the L5178Y mouse lymphoma forward mutation assay: V. Gases and vapors
Authors: McGregor Douglas , Brown Alison G. , Cattanach Pamela , Edwards Ian , McBride Douglas , Riach Colin , Shepherd Wendy , Caspary William J. , Van Zeeland A. A. 
Published: February 2007

AbstractA new protocol for testing vapors and gases in the L5178Y mouse lymphoma assay is presented. Four chemicals, propylene, 1,2‐propylene oxide, 1,3‐butadiene, and vinylidene chloride, were tested for their mutagenic potential. Cultures were exposed to the chemicals, which were delivered as vapors or gases, for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 μg/ml. Each chemical was tested at least twice. Significant responses were obtained with 1,2‐propylene oxide and vinylidene chloride, but neither cytotoxicity nor mutagenicity was induced by 1,3‐butadiene; propylene could not be classified as either mutagenic or non‐mutagenic in the assay. Rat liver S9 mix was not a requirement for the mutagenic activity of 1,2‐propylene oxide, whereas the liver preparation markedly enhanced both the cytotoxicity and mutagenicity of vinylidene chloride.
Induction of 6‐thioguanine‐resistant lymphocytes in fischer 344 rats following in vivo exposure to n‐ethyl‐n‐nitrosourea and cyclophosphamide
Authors: Aidoo Anane , Lyn‐Cook Lascelles E. , Mittelstaedt Roberta A. , Heflich Robert H. , Casciano Daniel A. , Cole J. 
Published: February 2007

AbstractWe have developed a limiting dilution clonal assay for determining the frequency of 6‐thioguanine‐resistant (TGr) lymphocytes produced in rats by in vivo exposure to genotoxic agents. Spleen lymphocytes were isolated from female Fischer 344 rats and were cultured with 1 μg/ml of phytohemagglutinin (PHA) for 40 hr. Northern blot analysis revealed that this procedure resulted in increased hprt and β‐actin mRNA synthesis. Conditions for optimum cloning were established by culturing four PHA‐primed lymphocytes/well in 96‐well round‐bottom microtiter plates containing a medium supplemented with interleukin‐2. These cultures also contained autologous and/or TK6 feeder cells inactivated with different doses of irradiation. Lymphocyte cloning efficiencies (CEs) were highest in plates containing both irradiated TK6 cells (5 × 103 cells/well; 90 Gy) and irradiated autologous feeder cells (5 × 104 cells/well; 50 Gy). CE did not depend on the number of primed lymphocytes/well when four or fewer target cells/well were cloned. To measure the effects of chemical mutagens on the frequency of TGr lymphocytes, rats were given a single i.p. injection of 0–150 mg/kg of N‐ethyl‐N‐nitrosourea (ENU), a direct‐acting alkylating agent, or 0–50 mg/kg of cyclophosphamide (CP), an indirect acting alkylating agent. Lymphocytes were isolated, primed, and cloned at 4 weeks after CP treatment and at 1, 2, 4 and 6 weeks after ENU treatment. CE in these cultures ranged from 12% to 27%. Cultures were also established for measuring CE in the presence of 6‐thioguanine (TG) and these contained 5 × 103 irradiated TK6 cells and 5 × 104 primed rat lymphocytes/well. The frequency of TGr lymphocytes was calculated by correcting the CE in the presence of TG with the CE measured in its absence. ENU exposure produced a higher frequency of TGr lymphocytes than CP, but both chemicals produced a dose‐dependent increase in TGr cells. In addition, the frequency of ENU‐induced TGr lymphocytes increased with time after treatment. The TGr cells are presumed to be hprt mutants, but further analysis at the DNA level is required to establish this. The dose‐dependent responses obtained with both ENU and CP treatments suggest that rat lymphocytes are sensitive to direct‐ and indirect‐acting alkylating agents administered in vivo and that the rat lymphocyte assay is a useful complement to the in vivo/in vitro mouse assay for determining the mutagenicity of environmental toxicants.
Dose‐dependent cytotoxic and mutagenic effects of antineoplastic alkylating agents on human lymphoblastoid cells
Authors: Sanderson Barbara J. S. , Johnson Kara J. , Henner W. David , Skopek T. R. 
Published: February 2007

AbstractThe alkylating agents in clinical use as antineoplastics are strongly implicated as human carcinogens on the basis of animal studies and human epidemiologic studies. However, there is little quantitative information on the extent to which exposure to these drugs is mutagenic for normal (non‐malignant) cells and the extent to which such mutagenicity correlates with cytotoxicity of these agents. Human lymphoblastoid cells (WIL2‐NS) were exposed to graded doses of eight antineoplastic alkylating agents. Cell killing and mutation induction at the hypoxanthine ‐guanine phosphoribosyltransferase (HPRT) locus were measured by cloning in microplates in the presence and absence of 6‐thioguanine. Dose‐dependent decreases in survival were used to calculate IC50s for each of the drugs tested. The IC50s, for 1 hr exposure, ranged from 4 × 10−7 M for nitrogen mustard to 5 × 10−4 M for busulfan. The eight drugs tested each induced detectable increases in the frequency of mutant cells. The mutagenicity of these agents is correlated strongly with cytotoxicity. However, at equitoxic doses (IC50), the frequency of induced mutants ranged from approximately 3 × 10−6 for 1,3‐bis(2‐chlorethyl)‐1‐nitrosourea (BCNU) to 2 × 10−5 for busulfan and cisplatin. These results quantitate the dose‐dependent cytotoxic and mutagenic effects of these bifunctional alkylating agents on human cells. All are cytotoxic and mutagenic, although their mutagenic efficiency varies.
Cigarette smoke‐induced dna adducts in the respiratory and nonrespiratory tissues of rats
Authors: Gairola C. Gary , Gupta R. C. , Reidy J. A. 
Published: February 2007

AbstractFormation of DNA adducts is regarded as an essential initial step in the process of chemical carcinogenesis. To determine how chronic exposure to cigarette smoke affects the distribution of DNA adducts in selected respiratory and nonrespiratory tissues, we exposed male Sprague‐Dawley rats daily to fresh mainstream smoke from the University of Kentucky reference cigarettes (2R1) in a nose‐only exposure system for 32 weeks. Blood carboxyhemoglobin, total particulate matter (TPM) intake, and pulmonary aryl hydrocarbon hydroxylase values indicated effective exposure of animals to cigarette smoke. DNA was extracted from three respiratory (larynx, trachea, and lung) and three nonrespiratory (liver, heart, and bladder) tissues and analyzed for DNA adducts by the 32P‐postlabeling assay under conditions capable of detecting low levels of diverse aromatic/hydrophobic adducts. Data showed that the total DNA adducts in the lung, heart, trachea, and larynx were increased by 10‐ to 20‐fold in the smoke‐exposed group. Five‐fold increase was observed in the bladder tissue, but differences were not present in the liver DNA of control and smoke‐exposed groups. These data suggest selective formation of DNA adducts in the tissues.
Evaluation of the SOS chromotest for the detection of antimutagens
Authors: Sato Takahiko , Chikazawa Kazuhiko , Yamamori Hidetomo , Ose Youki , Nagase Hisamitsu , Kito Hideaki , Nestman E. R. 
Published: February 2007

AbstractThe SOS chromotest was applied for the detection of antimutagens. To raise SOS induction, the bacteria were treated with the mutagens, UV, 4‐nitroquinoline N‐oxide (4NQO), N‐methyl‐N′‐nitro‐N‐nitroso‐guanidine (MNNG), or benzo[a]pyrene (B[a]p). The inhibitory effects of L‐ascorbic acid, glutathione, vanillin, 5‐fluorouracil (5‐FU), 5‐chlorouracil (5‐CU), cobaltous chloride, sodium selenite and sodium arsenite, which are known as antimutagens, were investigated with their addition either simultaneously or post treatment time.It became clear that the SOS chromotest was very useful for the detection of antimutagens.
Cytocidal and filamentous response of Escherichia coli cells exposed to low concentrations of hydrogen peroxide and hydroxyl radical scavengers
Authors: Brandi Giorgio , Salvaggio Leonardo , Cattabeni Flaminio , Cantoni Orazio , Mortelmans K. E. 
Published: February 2007

AbstractThe hydroxyl radical scavengers thiourea, ethanol, and dimethyl sulfoxide significantly reduced the killing of Escherichia coli elicited by low concentrations of H2O2 (resulting in mode 1 killing) when treatments with the oxidant and the scavengers were performed in a complete growth medium (K medium) but not in M9 salts. In addition, thiourea efficiently prevented the toxic response to high concentrations of H2O2 (resulting in mode 2 killing) under both exposure conditions. Sod A cells, which do not respond with a bimodal pattern of toxicity when challenged with increasing concentrations of H2O2, were markedly protected by thiourea against the lethal action of various levels of the oxidant (which in the wild‐type strain result in either mode 1 or mode 2 killing) under conditions of treatments in both K medium and M9 salts. In some experiments, wild‐type cells were challenged with a low concentration of H2O2 (in the absence or presence of hydroxyl radical scavengers) and then postincubated in fresh K medium for various time intervals. It was found that scavengers were able to inhibit the filamentous response generated by exposure to the oxidant in K medium. Both the length and the number of filaments were markedly reduced. Treatment in M9 salts resulted in a limited number of very short filaments, and this response was slightly reduced by the scavengers.
Inhibitory effect of lichen constituents on mutagenicity induced by heterocyclic amines
Authors: Osawa T. , Kumon H. , Reece C. A. , Shibamoto T. , Snyder R. D. 
Published: February 2007

AbstractPhysodic acid, one of the main constituents of Hypogymnia enteromorpha, inhibited the mutagenicity of indirect mutagens, including benzo[a]pyrene and heterocyclic amines in Salmonella typhimurium TA 98. In contrast, it was not effective against direct mutagens such as 6‐nitropiperonal and adriamycin. Its antimutagenicity was not associated with free‐radical scavenging or antioxidative activities. Physodic acid seemed to inhibit the formation of reactive metabolites, such as N‐hydroxy‐Trp‐P‐2, by blocking the hepatic microsomal oxidation systems. Another component of H. enteromorpha, physodalic acid, also inhibited mutagenicity of a heterocyclic amine, Trp‐P‐2, in S. typhimurium TA 98, even though it was reportedly mutagenic in S. typhimurium TA 100.
Genotoxicity of nitrated polycyclic aromatic hydrocarbons and related structures on Escherichia coli PQ37 (SOS chromotest)
Authors: Mersch‐Sundermann V. , Kern S. , Wintermann F. , Eisenstadt E. 
Published: February 2007

AbstractTo determine the genotoxicity of nitrated polycyclic aromatic hydrocarbons and related molecules (nPAH) we examined 24 compounds representative of nitroanthracenes, nitrofluorenes, nitronaphthalenes, nitropyrenes, and nitroquinolines for genotoxicity in Escherichia coli PQ37 (SOS‐chromotest). To enhance the sensitivity of the tester strain and optimize metabolic activation we used a modified test protocol and S9‐mix composition. All chemicals with the exception of 9‐nitroanthracene, 1‐ and 2‐nitronaphthalene, 2‐methyl‐1‐nitronaphthalene, and 5‐, 6‐, and 8‐nitroquinoline induced the SOS system of E. coli PQ37. As expected from previously referred mutagenicity studies, the highest SOS inducing potencies (SOSIP) were exhibited by the dinitropyrenes (SOSIP = 151–416), 4‐nitroquinoline‐N‐oxide (SOSIP = 62), and 3‐nitrofluoranthese (SOSIP = 16). Except for some nitronaphthalenes, the nPAHs showed their highest genotoxicity in the absence of an exogeneous metabolic activation system. The results were compared to those reported for the bacterial mutagenicity of these substances in Salmonella typhimurium TA98.
Comparison of Hprt variant frequencies and chromosome aberration frequencies in lymphocytes from radiotherapy and chemotherapy patients: A Prospective Study
Authors: Ammenheuser Marinel M. , Au William W. , Whorton Elbert B. , Belli James A. , Ward Jonathan B. 
Published: February 2007

AbstractThe autoradiographic 6‐thioguanine‐resistant mutant lymphocyte assay and a chromosome aberration assay were used to determine the time‐course of appearance and persistence of elevated frequencies of hprt variants and dicentric chromosomes in patients receiving x‐irradiation therapy. Twelve cancer patients, treated with 180–200 cGy/day, 5 days/wk, for 3–7 wk, were studied before treatment, at various weekly intervals during treatment, and after treatment. The hprt mutation assays were done with frozen/thawed lymphocytes isolated from aliquots of the same blood samples used for the chromosome aberration assays. The hprt variant frequencies (Vfs) of only 4 of the 7 patients assayed at 2 wk of treatment were elevated over pre‐treatment Vfs, but during the 3rd and 4th weeks of treatment there were significant (P < 0.01) 5‐ to 15‐fold increases in all Vfs. By 6–32 wk after treatment Vfs had fallen to levels only slightly higher than the mean pre‐treatment Vf. The frequencies of cells with dicentric chromosomes were significantly increased (P < 0.01) after 1 wk of radiotherapy, continued to increase during therapy, and remained elevated after treatment. Five multiple sclerosis patients were also studied before and at 2 and 4 wk intervals after treatment with monthly i.v. doses of 750 mg/m2 of cyclophosphamide (CP). There were no significant elevations in chromosome aberrations at these post‐treatment sample times. Previous assays for hprt mutants, done with aliquats of the same blood samples (Ammenheuser et al.: Mutat Res 204:509–520, 1988), had shown 8‐ to 20‐fold increases in Vfs 2 wk after the 1st CP treatment. Our results demonstrate the complementary nature of these two human monitoring assays and emphasize the importance of careful selection of optimal sampling times.