bluuebunny/crossref_metadata_2025_split huggingface dataset:
An E coli microsuspension assay for the detection of DNA damage induced by direct‐acting agents and promutagens
Authors: McCarroll N. E. , Piper C. E. , Keech B. H. 
Published: February 2007

AbstractWe have devised a microsuspension assay utilizing E coli indicator strains WP2, WP2 uvrA, WP67, CM611, WP100, W3110 polA+, and p3478 pola‐ for the detection of chemically‐induced preferential kill of repair‐deficient strains. Data are presented from tests of 77 compounds representing a wide range of chemical classes which demonstrate the efficiency of the E coli microsuspension assay as both a qualitative and quantitative screen of DNA‐modifying activity. Furthermore, the use of a battery of indicator strains lacking different repair systems offers the advantage of providing preliminary information concerning the mechanism of DNA damage induction by a test agent.
An examination of the quantitative suspension assay for mutagenesis with strains of salmonella typhimurium
Authors: Thompson E. D. , Melampy P. J. 
Published: February 2007

AbstractThe effects of cell toxicity on the mutagenic response obtained in a quantitative suspension assay using the strains of Salmonella typhimurium developed by Ames et al [Mutat Res 31:347–364, 1975] were examined. Cell toxicity was shown to produce false‐positive results when the cells were plated immediately with trace amounts of histidine in the overlay agar. Replacement of the overlay agar with one lacking histidine produced false‐negative results when the cells were plated immediately after exposure to a frame‐shift‐type mutagen. The inclusion of an overnight growth period in brain‐heart infusion broth before plating the cells on minimal medium permitted incorporation of mutations into the genome and also yielded constant titers. The addition of the regrowth period is shown to be necessary for obtaining valid results in a suspension assay.
Structural basis of the mutagenicity in bacteria of nitrated naphthalene and derivatives
Authors: McCoy Elena C. , Rosenkranz E. Joshua , Petrullo Lynn A. , Rosenkranz Herbert S. , Mermelstein Robert 
Published: February 2007

AbstractWhile 2‐nitronaphthalene was a weak direct‐acting base‐substitution mutagen (1.4 revertants/nanomole) for Salmonella typhimurium, the analogous nitronaphthalic acid anhydride and imides were moderate frameshift mutagens (∼20 rev/nanomole in strain TA98). Although imide derivatives are efficient DNA intercalators, mutagenicity data indicate that the bulk of the frameshift activity is derived from adduct formation between hydroxylamine intermediates and DNA. The low level of frameshift activity (∼8% of total) resulting from simple intercalation (measured in strain TA1537) is not dependent upon reduction of the nitro function.Evidence is presented that suggests that the reduction of the nitro function to the corresponding hydroylamine might not involve a free nitroso intermediate.The introduction of a second nitrofunction into nitronaphthalenes results in great positional effects of the various isomers on mutagenic activity and specificity.
Chromosome changes in human lymphocytes after separate and combined treatment with divalent salts of lead, cadmium, and zinc
Authors: Gasiorek K. , Bauchinger M. 
Published: February 2007

AbstractUnstimulated human lymphocytes in whole blood were treated for three hours with lead, cadmium, and zinc acetate separately and in combinations of two or three metal salts with different concentrations of between 10−3 and 10−8 moles, respectively. Untreated cultures and sodium acetate‐treated samples served as controls. Chromosome analysis from 48 cultures revealed higher incidences of chromatid‐type aberrations and gaps only for cultures exclusively treated with cadmium. The results are discussed under the aspect of heavy metal metabolism in human lymphocytes.
Mutagenicity of municipal water obtained from an agricultural area
Authors: Heartlein M. W. , Demarini D. M. , Katz A. J. , Brockman H. E. , Means J. C. , Plewa M. J. 
Published: February 2007

AbstractWe have studied the mutagenicity of the water from Lake Bloomington and of the tap water that is made from the lake water. The lake, which is the source of drinking water for Bloomington, Illinois (pop. 44,000), is surrounded by land that is farmed intensively ‐ being mainly in maize and soybeans. Samples were collected monthly from May through October 1979 and concentrated 3,000× with XAD‐2 resin. Nearly all of the lake and tap water concentrates were mutagenic in Salmonella typhimurium TA98 and TA100 in the presence of S‐9 mix, and the May tap water concentrate was highly mutagenic. In addition, many of the concentrates were toxic to the bacteria in the absence of S‐9 mix. Chemical analysis of the highly mutagenic tap water concentrate from May revealed the presence of a number of organic contaminants that were absent from control concentrates prepared from deionized and distilled treated well water. In addition, unconcentrated lake and tap water were tested in a reverse‐mutation test in maize (Zea mays); no mutagenicity was detected. This study indicates that the contamination of drinking water with agricultural and/or industrial chemicals may result in a potential health hazard.
Characterization of a rat lymphocyte culture system for assessing sister chromatid exchange after in vivo exposure to genotoxic agents
Authors: Kligerman A. D. , Wilmer J. L. , Erexson G. L. 
Published: February 2007

AbstractLymphocyte culture systems have the major advantage of permitting the analyssis of in vivo cytogenetic damage with minimal injury to the animal under study. This paper describes a rat lymphocyte culture system designed for the study of sister chromatid exchange (SCE) induced by in vivo exposure to genotoxic agents. A standard protocol was established in which 1 to 2 ml of blood are removed from rats by cardiac puncture, washed three times with phosphate‐buffered saline (pH 7.4), and grown in RPMI 1640. 5‐Bromodeoxyuridine (BrdU) (1.0 μM) is added after 24 hr, and cells are harvested after 56 hr of culture. Critical steps for successful blast transformation include washing the blood in buffered saline and the adding of 2.0 to 4.0 μg phytohemagglutinin/ml to the culture medium. The use of low concentrations of BrdU (≤5.0 μM) is recommended to maintain low baseline SCE levels and to avoid cytotoxicity. The mutagenic carcinogen, ethyl methanesulfonate (EMS), was used as a positive control agent and at a dose of 300 mg/kg caused a fourfold increase in SCE frequency. Twenty‐eight days after EMS administration (30, 100, 300 mg/kg), lymphocytes from treated animals still displayed SCE levels at least 50% above baseline. This system provides a reliable means of investigating chemically induced SCE in the rat.
Radiosterilization of rat liver microsome containing postmitochondrial supernatant for mutation assays
Authors: Barfknecht Thomas R. , Andon Barbara M. , Bishop Walter W. , Thilly William G. 
Published: February 2007

AbstractGamma‐irradiation was effectively employed to sterilize rat liver postmito‐chondrial supernant (PMS), which is required for the metabolic activation of soots and soot‐derived polycyclic aromatic hydrocarbons to mutagens. When a known number of Bacillus subtilis spores were added to the PMS and gammairradiated at −80° C, a 2‐Mrad dose resulted in a 7.5 log kill of the spores. A dose of 3 Mrads was selected as a sufficient effective sterilizing dose and had no significant effect upon the ability of gamma‐irradiated PMS to metabolically activate diesel soot and two diesel soot components, benzo(a)pyrene and fluoranthene to mutagens in a Salmonella typhimurium 8‐azaguanine resistance forward mutation assay. Three Mrads of gamma‐irradiation also had no effect upon the ability of PMS to activate benzo[a]pyrene to a mutagen for the human lymphoblasts. However, gamma‐irradiation did reduce the ability of PMS to activate dimethylnitrosamine to a mutagen for S typhimurium.
Regression analysis of ames test data
Authors: Myers Lawrence E. , Sexton Nancy H. , Southerland Leslie I. , Wolff Thomas J. 
Published: February 2007

AbstractWeighted least squares estimation is used for fitting nonlinear models to Ames test data. The models are biologically plausible, incorporating mutagenicity, toxicity, and/or saturation. Regressions are weighted to compensate for variance that changes with mean and to attain outlier resistance.
Comparison of the genetic activity of AF‐2 and nitrofurantoin in log and stationary phase cells of saccharomyces cerevisiae
Authors: Callen D. F. 
Published: February 2007

AbstractThe effects of nitrofurantoin and AF‐2 in stationary phase cells were compared with the effects in log phase cells. The Saccharomyces cerevisiae diploid strain D7 was used. This strain can be used to monitor lethality, gene conversion, mitotic gene recombination, and reversion. Stationary phase cells were not sensitive to nitrofurantoin, but treatment of log phase cells did result in the induction of lethality and gene conversion. Log phase cells were approximately 10 times more sensitive to the lethal effects of AF‐2 than were stationary phase cells. The AF‐2 induced increase in frequencies of gene conversion and mitotic recombination per surviving cell were similar in both log and stationary phase cells. Gene reversion was induced by AF‐2 in stationary cells, but no revertants were induced in log cells. Measurement of nitroreductase activity gave values for log phase cells which were five to sixfold greater than for stationary phase cells. The increased sensitivity of log phase cells to nitrofurans could therefore be in part due to an increased activation of these compounds. It is concluded that the use of log phase cells is optimal for the detection of induced gene conversion and recombination by nitro compounds.
Uptake and mutagenicity of AF‐2 in chinese hamster V‐79 spheroids under aerobic and hypoxic conditions
Authors: Olive Peggy L. , Durand Ralph E. 
Published: February 2007

AbstractChinese hamster V‐79 cells, when grown in suspension culture as multicell spheroids, display many of the features of organized tissue. AF‐2, a known mutagen, was used to examine the influence of some of these factors on mutagenesis. Since AF‐2 is fluorescent, FCM quantitation of intracellular drug content was performed after incubation of spheroids under either aerobic or hypoxic conditions. For the same level of toxicity, hypoxic spheroids accumulated twice as much AF‐2 as aerobic spheroids, but showed less than half the number of mutants resistant to 6‐thioguanine. Using velocity sedimentation techniques, a selective increase in the toxic and mutagenic effects of AF‐2 was found for internal vs external cells of the spheroids. However, in mutagenicity experiments using all the cells from spheroids, the response of the external cycling cells predominated over the response of the internal cells. Thus, in addition to the demonstration that cellular environment can modify mutagenesis, these results also suggest that the growth fraction of the target cells can be an important consideration in mutation experiments.
Mutagenicity and toxicity of aflatoxin precursors
Authors: Dunn J. J. , Lee L. S. , Ciegler A. 
Published: February 2007

AbstractThe Salmonella/microsome test and the chick embryo test were used to determine the mutagenicity and toxicity of five aflatoxin B1 precursors. A definite pattern emerges: the nearer to B1 an intermediate appears in the biosynthetic pathway, the more potent is its mutagenicity and toxicity.
The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells
Authors: Cohen Maimon M. , Simpson Stacy J. 
Published: February 2007

AbstractBleomycin, a radiomimetic glycopeptide, inhibits de novo DNA synthesis in ataxia telangiectasia lymphoblastoid B cells to a markedly lesser extent than in normal and xeroderma pigmentosum lymphoid cells. This observaton is similar to that following ionizing radiation; however, the effect is slower following the chemical treatment. Recovery of the normal cells occurs 15–18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24‐hour observation period. Similar differences were not observed following treatment with mitomycin C, a bifunctional alkylating agent, indicating a specific effect of bleomycin on DNA synthesis in ataxia telangiectasia cells. Following bleomycin treatment and preincubation with hydroxyurea, residual DNA synthesis in ataxia telangiectasia cells was similar to that in both normal and xeroderma pigmentosum lymphoid lines, suggesting that the capacity to repair the induced DNA lesion is present.
The use of primary rat hepatocytes to achieve metabolic activation of promutagens in the chinese hamster ovary/hypoxanthine‐guanine phosphoribosyl transferase mutational assay
Authors: Bermudez Edilberto , Couch David B. , Tillery Deborah 
Published: February 2007

AbstractA method is described in which primary rat hepatocytes have been cocultured with Chinese hamster ovary (CHO) cells to provide metabolic activation of promutagens in the Chinese hamster ovary/hypoxanthine‐guanine phosphoribosyl transferase (CHO/HGPRT) mutational assay. Single cell hepatocyte suspensions were prepared from male Fischer‐344 rats using the in situ collagenase perfusion technique. Hepatocytes were allowed to attach for 1.5 hours in tissue culture dishes containing an approximately equal number of CHO cells in log growth. The cocultures were exposed to promutagens for up to 20 hours in serum‐free medium. The survival and 6‐thioguanine‐resistant fraction of treated CHO cells were then determined as in the standard CHO/HGPRT assay. Aflatoxin B1 (AFB1) 7,12‐dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (B(a)P) were found to produce increases in the mutant fractions of treated CHO cells as a function of concentration. The time required for optimum expression of the mutant phenotype following exposure to DMBA and AFB1 was approximately 8 days. Primary cell‐mediated mutagenesis may be useful in elucidating metabolic pathways important in the production and detoxification of genotoxic products in vivo.
Mutagenic activity of sterilization indicators
Authors: Atherholt Thomas B. , McGarrity Gerard J. , Louis Judith 
Published: February 2007

AbstractUsing the Ames Salmonella/microsomal assay, mutagens were detected in acetone‐methylene chloride extracts of black threads on glass tube‐type sterilization indicators used in hospitals and research laboratories. Extracts of samples of commercially available black thread also contained mutagenic substances. Fluids autoclaved with these sterilization indicators may alter the results in mutagenicity and other studies.
Morphological transformation of C3H/10T1/2 CL8 cells by procarcinogens
Authors: Oshiro Y. , Balwierz P. S. 
Published: February 2007

AbstractIn order to increase the sensitivity of the C3H/10T1/2 CL8 (10T1/2) cell transformation system, we increased the chemical exposure period to a total of 6 days (two consecutive 3‐day exposures). Using this modified procedure, we transformed 10T1/2 cells with procarcinogens such as aflatoxin B1, benz(a)anthracene, and 4‐nitroquinoline‐1‐oxide which have been negative in the standard 10T1/2 cell transformation assay. However, β‐naphthylamine was inconclusive and 2‐acetylamino‐fluorine was negative in this modified assay system. Our results demonstrate that a simple modification of the 10T1/2 cell transformation method can increase the sensitivity to some procarcinogens that require metabolic activation.
Sister chromatid exchange response of human diploid fibroblasts and chinese hamster ovary cells to dimethylnitrosamine and benzo(a)pyrene
Authors: Tomkins Darrell J. , Kwok S. Emily , Douglas George R. , Biggs David 
Published: February 2007

AbstractIn the search for relevant assays for mutagenicity testing, considerable attention has been given to the use of mammalian cells in vitro and the incorporation of metabolic activation in the protocol. Chinese hamster ovary (CHO) cells are commonly chosen as the target cells for cytogenetic tests because of their excellent growth characteristics and long lifespan in culture. However, there may be cellular factors affecting the uptake, metabolism, and repair of damage which are not the same in all cell lines. The response of CHO cells and three human diploid fibroblast strains (IMR‐90, WI‐38, S‐3299) to benzo(a)pyrene (BP) and dimethylnitrosamine (DMN) were compared using sister chromatid exchange (SCE) analysis as a measure of genetic damage. For both BP and DMN the human cells and the CHO cells showed dose‐response slopes that were significantly different from zero, except CHO cells treated with BP for 1 hr and S‐3299 cells treated with DMN. Whereas human and CHO cells showed similar dose‐responses to BP and the three human cell strains had similar dose‐responses to BP and DMN, the dose‐response of the human cells to DMN was statistically less significant than that of CHO cells. Reducing the duration of chemical treatment in CHO cells had no effect on the slope of the dose‐response curves for BP or DMN. The observed differences between human and CHO cells may reflect differences in the fate of metabolic intermediates of DMN.
Restitution of chromatid and isochromatid breaks induced in the G2 phase by actinomycin D
Authors: Cherry Lorraine M. , Hsu T. C. 
Published: February 2007

AbstractAlthough actinomycin D (AMD) appears to cause chromatid breakage, it has been suggested that it merely weakens the chromosomal proteins, causing breaks to occur during the stress of fixation. To determine if this was true, we examined lymphocytes treated with AMD (3.5 μg/ml) for 90 min prior to harvesting for evidence of DNA repair. Besides single chromatid breaks, we observed a high frequency of chromatid exchange figures (translocations, inversions, rings) and closed isochromatid breaks, indicating that a type of DNA repair leading to chromosome aberrations had occurred prior to cell fixation. Therefore, at least some of the breaks observed after AMD treatment in G2 represented true DNA damage and were not merely artifacts of fixation.
Sister chromatid exchange induction in two cell lines
Authors: Mitchell Gillian A. , Meher‐Homji K. M. , Baker R. S. U. 
Published: February 2007

AbstractSister chromatid exchange (SCE) induction by the procarcinogen benzo (a)‐pyrene (BP) was studied using two established cell lines. Chinese hamster ovary (CHO) and Chinese hamster lung (Don) cells were exposed to varying concentrations of BP in the presence and absence of a rat liver metabolizing system. Results showed a significant difference in the abilities of the two cell lines to induce SCE in the absence of liver homogenate. These experiments demonstrate that Don cells are capable of generating active metabolites from biologically inactive procarcinogens presumably due to an inherent metabolizing system which is deficient or absent in CHO cells.
Mutagenicity of (R) and (S) styrene 7,8‐oxide and the intermediary mercapturic acid metabolites formed from styrene 7,8‐oxide
Authors: Pagano Dennis A. , Yagen Boris , Hernandez Oscar , Bend John R. , Zeiger Errol 
Published: February 2007

AbstractWe have tested the two enantiomers of styrene 7,8‐oxide and various thioether metabolites of racemic styrene 7,8‐oxide for their direct mutagenicity in Salmonella typhimurium TA100. The mutagenicity data suggests that the (R) enantiomer is more mutagenic than the (S) enantiomer, with the racemic mixture intermediate between the two. The thioether metabolites were not mutagenic. The difference in the mutagenicities of enantiomers probably resulted from a stereoselective process in the Salmonella tester strain. At the present time it is not clear whether the rate‐limiting reaction is the interaction of the enantiomers with DNA or some other cellular component.
In vivo and in vitro genotoxicity of three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine)
Authors: De Flora S. , Zanacchi P. , Bennicelli C. , Camoirano A. , Cavanna M. , Sciabà L. , Cajelli E. , Faggin P. , Brambilla G. 
Published: February 2007

AbstractThree antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine) were found to be genotoxic in four in vivo or in vitro short‐term test systems, a) In mice, a single ip administration of the LD50 of the three drugs caused a small but statistically significant increase over controls in DNA elution rate, ie, a modest amount of DNA fragmentation, in three of the four organs (liver, lung, kidney, and spleen) tested, DNA damage being absent in lung for hydralazine and endralazine and in liver for dihydralazine. Only for hydralazine DNA lesions were always repaired within 12 hr, in agreement with the constant lack of cumulative effects in mice given five successive daily doses. The rank of potencies was hydralazine< dihydralazine<endralazine. b) In mice bone marrow cells, all three hydrazine derivatives induced a modest but statistically significant increase over controls in the frequency of sister chromatid exchanges, the rank of potencies being in this case dihydralazine < endralazine < hydralazine. c) In the Ames reversion test all three drugs behaved as direct‐acting mutagens of low potency, whose activity was not influenced by rat liver nor by mouse liver or lung S‐9 fractions. Hydralazine and dihydralazine elicited mixed genetic mechanisms of mutations, while endralazine exclusively induced frameshift errors in Salmonella DNA. The recently developed strain TA97 was the most efficient in revealing frameshift errors with all three drugs. d) The selective lethality assays in a battery of two S typhimurium and five E coli strains confirmed the direct genotoxicity of hydralazine, dihydralazine, and endralazine, in order of potency. Potency was evaluated by means of a sensitive and reliable micromethod procedure. Among those investigated, the recA recombination repair and the lexA post‐replication repair (“SOS functions”) and, to a lesser extent, also the polymerase I mechanism, appeared to contribute to the specific DNA repair with all three drugs, while excision repair systems (uvrA and uvrB) did not appear to be involved.
Cytogenetic effects of shale‐derived oils in murine bone marrow
Authors: Meyne Julianne , Deaven L. L. 
Published: February 2007

AbstractThe cytogenetic effects of exposure of mice to shale‐derived oils by either skin painting or intraperitoneal injection were examined. Skin painting with 40 mg crude oil every other day for five weeks had no effect on the frequency of chromosomal aberrations observed in the bone marrow. Three daily intraperitoneal injections of 0.5–2.0 ml/kg per day of a crude shale oil from an aboveground retort induced a dose‐related increase in the frequency of aberrations observed. A hydrotreated sample of this oil produced a similar pattern of aberration induction, but at lower frequencies. Crude shale oil from a modified in situ retort induced the highest frequency of chromosomal aberrations at the 0.5 ml/kg dose; lower frequencies were induced at the 1.0 ml and 2.0 ml/kg doses. Of the three shale oils tested, only the crude oil from the aboveground retort induced increased frequencies of sister chromatid exchanges and only at doses that also induced structural aberrations. These studies indicate that structural aberration analysis is a more sensitive test than sister chromatid exchange analysis for the type of DNA damage induced by shale‐derived oils in murine bone marrow cells.