bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutagenicity of 2‐ and 3‐carbon halogenated compounds in the salmonella/mammalian‐microsome test
Authors: Stolzenberg S. J. , Hine C. H. 
Published: February 2007

AbstractShort‐chain, 2‐ and 3‐carbon halogenated hydrocarbons were tested for mutagenicity for Salmonella typhimurium strain TA 100 both with and without the presence of S‐9. Without exception, all brominated derivatives were more mutagenic than the chlorinated derivatives, usually by a substantial order of magnitude. 2‐Fluoroethanol, the only fluorinated compound tested, showed little or no mutagenic activity up to 100 μmole per plate concentration. Two highly purified propane derivatives containing a halogen atom on each of the three carbons showed little or no direct mutagenic activity. A third trihalogenated compound with a halogen atom on each carbon atom showed some direct mutagenic activity, probably due to impurities. However, all three trihalogenated compounds were highly active mutagens following S‐9 activation. The presence of a double bond in the case of 1,2,3‐trichloropropene resulted in a higher level of direct mutagenic activity than 1,2,3‐trichloropropane, but activation with S‐9 resulted in a further increase in mutagenic activity with the former compound. On the other hand, S‐9 caused a substantial decrease in mutagenic activity of most compounds containing a double bond. With the presence of an alcoholic group in a compound, the addition of S‐9 caused variable responses, increasing the number of his+ revertant colonies due to 2,3‐dibromopropanol but had little or no effect with five other compounds containing an alcoholic group. Evidence is also presented that the position of a double bond in relation to the halogen atoms may influence mutagenic activity.
Ii. Comparative extraction of houston air particulates with cyclohexane or a mixture of benzene, methanol, and dichloromethane
Authors: Preidecker Barbara Lee Borns 
Published: February 2007

AbstractA recent study (see preceding article) was conducted to evaluate bacterial mutagenicity of extracted particulates collected from air in Houston, Texas. Initially the solvent system used to extract these particulates was the 1:1:1 v/v mixture of benzene, methanol, and dichloromethane used by Pitts et al [1] in a similar study in California. Because of recent concern about the genetic toxicity of benzene, efforts are being made, where possible, to substitute other solvents, and a suggestion was made to try cyclohexane.The recent National Institute for Occupational Safety and Health (NIOSH) documents on exposure to coal tar [2] and to asphalt fumes [3] have recommended use of cyclohexane to extract air samples from occupationally exposed air filters. In addition, recent publications [4–6] have used cyclohexane to extract polyaromatic hydrocarbons (PAH) and aliphatic hydrocarbons from particulate air samples. A study done by Stanley et al [7] found cyclohexane almost 100% efficient at extracting benzo(a)pyrene. The present study was designed to examine the difference in efficiency of extraction between cyclohexane and a 1:1:1 mixture of benzene, methanol, and dichloromethane, using the Ames assay as a test for mutagenicity.
X irradiation and sister chromatid exchange in cultured human lymphocytes
Authors: Morgan William F. , Crossen Peter E. 
Published: February 2007

AbstractSister chromatid exchange (SCE) frequency was not increased in G0 lymphocytes following irradiation up to 400 rads. Lymphocytes irradiated after 42 or 60 hours of culture showed a dose‐dependent increase in exchange frequency at 100 and 200 rads. SCE was not increased in cells irradiated in G2 (68.5 hours).Lymphocytes maintained in a 5‐Bromodeoxyuridine (BrdUrd) free medium and irradiated 42 hours after culture initiation showed an increase in SCE if BrdUrd was added immediately after irradiation, but no increase was found if there was a 5 hour holding period prior to the addition of BrdUrd.The effect on induced SCE frequency of heightened radiosensitivity due to increased amounts of BrdUrd was also investigated. When the BrdUrd concentration was increased from 10 μg/ml to 50 μg/ml, the percent increase in X‐ray‐induced SCE was lower at 50 μg/ml. In addition, increased BrdUrd concentration only slightly increased the sensitivity of the SCE technique to irradiation doses of 50 rads.
Sunlight‐induced mutagenesis and toxicity in L5178Y mouse cells: Determination and comparison with other light sources
Authors: Krell Kenneth , Jacobson Elizabeth D. 
Published: February 2007

AbstractCompared on the basis of equal exposure, in joules per square meter (J/m2) the mutagenic and toxic effects in L5178Y mouse lymphoma cells of radiation emitted by some fluorescent lamps and a sunlamp are quantitatively similar to solar radiation effects at the earth's surface. When the relative intensities of radiation are taken into account, the artificial light sources range from 8 to 1 /222 times as mutagenic and 4.1 to < 1 /99 times as toxic as sunlight.
Clastogen‐induced micronuclei in peripheral blood erythrocytes: The basis of an improved micronucleus test
Authors: MacGregor James T. , Wehr Carol M. , Gould Daniel H. 
Published: February 2007

AbstractMicronuclei induced in bone marrow erythroblasts by clastogenic chemicals are easily detected in peripheral blood. In mice treated with nitrogen mustard, 7,12 dimethylbenz(a)anthracene, or cyclophosphamide, the peak incidence of micronucleated polychromatic erythrocytes in peripheral blood was at least as great as the maximum incidence in bone marrow. In each case the peak incidence in blood occurred on the day following the peak incidence observed in bone marrow. Thus, for general genetic screening purposes, monitoring micronuclei in peripheral blood rather than in bone marrow smears provides at least equal sensitivity, offers greater simplicity in sample preparation and scoring, permits multiple sampling of treated animals, and may also facilitate automated scoring and human cytogenetic monitoring.
The evaluation of the epoxide diluent, n‐butylglycidyl ether, in a series of mutagenicity assays
Authors: Connor T. H. , Ward J. B. , Meyne J. , Pullin T. G. , Legator M. S. 
Published: February 2007

AbstractThe epoxide diluent, n‐butylglycidyl ether (n‐BGE), was tested in vitro for mutagenicity using Salmonella typhimurium and for transforming ability in mouse embryo cells (Balb/3T3‐A31‐1‐13). The n‐BGE produced base‐pair type mutations in S typhimurium strains TA1535 and TA100. However, it failed to transform mouse embryo cells when assayed up to toxic levels. The mutagenic activity could not be detected in the urine of mice, although several doses, routes of administrations, and lengths of exposure were examined. Orally adminsitered n‐BGE did not produce any increase in micronuclei in mice, but when the diluent was administered intraperitoneally, either one or two times, dose‐related increases in the number of micronuclei were observed.
Chemically‐induced unscheduled DNA synthesis in primary rat hepatocyte cultures: A comparison with bacterial mutagenicity using 218 compounds
Authors: Probst Gregory S. , McMahon Robert E. , Hill L. E. , Thompson Christina Z. , Epp J. K. , Neal S. B. 
Published: February 2007

AbstractThe autoradiographic identification of unscheduled DNA synthesis (UDS) in primary cultures of adult rat hepatocytes (HPC) has been proposed as a predictive test for mutagens/carcinogens. To assess the predictive value of this test, results in the hepatocyte UDS assay were compared with data for bacterial mutagenicity using a modified Ames test. Over 200 compounds representing a variety of chemical classes consisting of procarcinogens, ultimate carcinogens, and noncarcinogens were tested in each system. The accurate discrimination of many carcinogens/noncarcinogens was demonstrated by both systems. The induction of UDS in hepatocytes showed an excellent correlation with bacterial mutagenesis in response to polycyclic aromatic hydrocarbons, aromatic amines, biphenyls, nitrosamines, carbamates, azo‐compounds, acridines, halogenated compounds, nitrosureas, quinolines, pyridines, purines, pyrimidines, esters and carbamates. Nitrocompounds, although active in bacteria, were poor inducers of UDS. The results support the complementary and confirmatory nature of these tests for genotoxic chemicals and indicate the usefulness of the hepatocyte UDS system as a component in a battery of short‐term predictive tests for mutagens/carcinogens.
Induction of sister chromatid exchanges in human diploid fibroblasts by mutagens with and without rat liver microsomal activation
Authors: Yang D. P. , Graupensperger F. , Minecci L. C. , Rubin B. A. 
Published: February 2007

AbstractThe frequency of sister chromatid exchange (SCE) in WI‐38 cells was estimated by the 5‐bromodeoxyuridine (BrdUrd)‐dye technique after one hour's exposure to cyclophosphamide (CY), N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), 4‐nitroquinoline‐1‐oxide (4NQO), and maleic hydrazide (MH) with and without the addition of rat liver microsomal suspension (S‐9) fraction with co‐factors (S‐9 mix). CY at concentrations from 1 × 10−5M to 1 × 10−3M with S‐9 mix increased the number of SCEs per cell in a dose‐dependent manner. Without S‐9 mix, CY at concentrations below 1 × 10−3M failed to produce more SCEs than the controls. MNNG at 1 × 10−8M and 4NQO at 1 × 10−7M without S‐9 produced significant increases in SCEs per cell. Addition of S‐9 during treatment slightly decreased the effects of MNNG and 4NQO in the formation of SCEs. MH was tested at pH 6.4 and pH 7.6. At pH 7.6, MH at 1 × 10−3M without S‐9 mix inhibited cell multiplication, but did not cause a significant increase of SCEs per cell. There were no interactions between MH (2 × 10−4M) and S‐9 mix nor between MH and the pH levels tested. These results indicate that in the presence of metabolic activation, SCE formation in human diploid fibroblasts in vitro may be used as a potential assay for mutagenicity.
Perspectives in mutagenesis
Authors: Malling Heinrich V. 
Published: February 2007

AbstractI would first like to thank the Environmental Mutagen Society for honoring me with its 1980 award; I also would like to take this opportunity to acknowledge all the people who have worked with me and helped me since I started my work in mutagenesis in 1953. I feel especially indebted to my wife, Martha, whose support has been absolutely essential for my career.I would now like to explore some important problems in environmental mutagenesis. Obviously, I cannot touch upon new developments in all aspects of environmental mutagenesis ‐ a field that has become increasingly broad in recent years. As in the past, there continue to be major advances in understanding mechanisms of mutagenesis, developing short‐term tests, characterizing mutations, elucidating the relationship between mutagenesis and carcinogenesis, understanding the metabolism of mutagens, and many other areas. Many of these advances are reflected in the contents of the papers, symposia, and poster sessions of this meeting. In the years that I have been involved in mutation research and environmental mutagenesis, my interests and research activity have spanned a number of these areas; and I am pleased by the recent progress that I see taking place in them. In this talk, however, I would like to direct my comments toward a rather new dimension in environmental mutagenesis in which I have become increasingly interested: The monitoring of mutations in the human population.In the monitoring of the human population there are two choices: We can monitor the progeny of an exposed population or we can consider exposed persons as populations of cells and measure the mutant frequency in individual cells in these persons. Technical developments are advancing rapidly in both of these approaches. The pioneering work of James Neel in measuring germinal effects of mutagens in the human population is well known [Neel, 1970]. Methods for measuring mutation frequencies in single cells in vivo also are beginning to be available. For instance, Strauss and Albertini [1979] are developing a system to detect HGPRT mutants in human lymphocytes. Of course, there are still difficult problems to be resolved in this system; and we do not know with certainty.
Evaluation of the release of mutagens from diesel particles in the presence of physiological fluids
Authors: King Leon C. , Kohan Mike J. , Austin Ann C. , Claxton Larry D. , Huisingh J. Lewtas 
Published: February 2007

AbstractThe Ames Salmonella typhimurium plate incorporation assay was used to evaluate the mutagenicity of organics extracted from diesel exhaust particles. Organic solvents were more efficient than physiological fluids in removing mutagens from diesel particles, with dichloromethane extracts having the greatest mutagenic activity of the solvents examined. Serum and lung cytosol were more effective than acellular lung lavage fluid in releasing mutagenic activity from diesel particles. The mutagenic activity of diesel particle organics preextracted with dichloromethane is greatly reduced upon the addition of serum and lung cytosol to organics. Subsequently, incubation of protease with serum and lung cytosol‐bound diesel organics increases the mutagenic activity. Fluorescence intensity was quantitated and found to correlate with mutagenic activity in the organic and serum extracts, but not the lung cytosol extracts. These studies suggest that substantial mutagenic activity is released from diesel particles upon incubation with serum and lung cytosol.
Cytotoxic and mutagenic properties of shale oil byproducts I. Activation of retort process waters with near ultraviolet light
Authors: Strniste Gary F. , Chen David J. 
Published: February 2007

AbstractCultured Chinese hamster ovary (CHO) cells were exposed to dilutions of shale oil retort process waters obtained from three different retorting processes located in the Green River oil shale formations in the western part of the United States. Although the intensity of the response was dictated by the process water used, all induced a cytotoxic (reduction in colony‐forming ability) and mutagenic (induced at the hypoxanthine‐guanine phosphoribosyl transferase (HGPRT) locus) response in cells pretreated with dilutions of the waters and subsequent exposure to near ultraviolet light (NUV). Combinations of process water plus NUV yielded mutation frequencies as great as 50% that witnessed for the mutation frequency induced by the potent carcinogen far ultraviolet light. NUV alone was nontoxic and nonmutagenic at the doses of radiation used. Exposure of CHO cells in the dark to nontoxic dilutions of the process waters resulted in small but significant increases in 6‐thioguanine resistant mutants (1–2 times background rates). The biological consequences resulting from the disposal of retort process waters into the delicate environment present in this oil shale region could be further complicated by this photoactivating process.
Cytotoxicity and mutagenicity of the fungicides captan and folpet in cultured mammalian cells (CHO/HGPRT system)
Authors: O'neill J. Patrick , Forbes Nancy L. , Hsie Abraham W. 
Published: February 2007

AbstractThe cytotoxicity and mutagenicity of the fungicides captan and folpet were determined in the CHO/HGPRT system which utilizes Chinese hamster ovary cells and resistance to 6‐thioguanine to estimate mutation induction at the hypoxanthine‐guanine phosphoribosyl transferase locus. Treatment of cultures with each compound for 5 hr in serum‐free medium resulted in reproducible, significant, concentration‐dependent increases in the frequency of 6‐thioguanine‐resistant mutants.
Anaphase aberrations: A measure of genotoxicity in mutagen‐treated fish cells
Authors: Kocan R. M. , Landolt M. L. , Sabo K. M. 
Published: February 2007

AbstractRainbow trout gonad cells (RTG‐2) were cultured for various lengths of time in the presence of several classes of known mutagenic chemicals and several related compounds that possessed no known mutagenic/carcinogenic activity. During the course of exposure the cells were examined for the presence of abnormalities in the chromosome arrangement of anaphase figures during mitosis. Untreated and solvent‐treated (dimethylsulfoxide‐treated) cells exhibited a background abnormality rate of 12% with only minor chromosomal defects being observed. This was also true for those cells exposed to naphthol and anthracene, two chemicals with no proven mutagenic or carcinogenic activity. Conversely, significant increases in the frequency of anaphase aberrations were produced in cells treated with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, benzo(a)pyrene, 9‐aminoacridine and mitomycin‐C. These abnormalities were also far more complex and extensive than those observed in the control and nonmutagen‐treated cells. Many species of fish have extremely small and numerous chromosomes, making resolution of chromosome defects such as sister chromatid exchange and deletions more difficult than in most mammalian diploid cells, which generally have larger and fewer chromosomes. Examination of cells during anaphase eliminates the need to observe each chromosome separately as well as the need to produce well‐spread metaphase chromosomes. Since the sensitivity of anaphase aberrations to known mutagenic/carcinogenic compounds appears to be quite high in trout cells and since hundreds of suitable cells are available for analysis, this may be an appropriate alternative or addition to some of the more standard chromsosome macrolesion tests developed in mammalian systems.
Effect of diesel exhaust emissions, particulates, and extract on sister chromatid exchange in transplacentally exposed fetal hamster liver
Authors: Pereira Michael A. , McMillan Lofton , Kaur P. , Gulati D. K. , Sabharwal P. S. 
Published: February 2007

AbstractThe genotoxic activity of diesel exhaust emissions, particulate matter, and an organic extract of the particulate matter was evaluated in transplacentally exposed Syrian hamster fetal liver cells. The frequency of sister chromatid exchange (SCE) was determined on day 13 of gestation. The extract of diesel particulate matter caused a dose‐dependent increase in the frequency of SCE with a doubling in the incidence above 320mg/kg. The diesel particulate matter and diesel exhaust emissions did not alter the frequency of SCE. The extract and particulate matter did cause a dose‐dependent decrease in the mitotic activity of the fetal liver. The in utero SCE analysis was demonstrated to be a sensitive assay for determination of the genotoxic activity of a complex mixture in transplacentally exposed fetuses.
Comparison of microsomal inducer pretreatment on the in vitro α‐hydroxylation and mutagenicity of N‐nitrosopyrrolidine in rat and hamster liver
Authors: McCoy G. David , Hecht Stephen S. , McCoy Elena C. 
Published: February 2007

AbstractThe effect of modifiers of liver mixed function oxidase activity on the in vitro α‐hydroxylation and mutagenicity of N‐nitrosopyrrolidine (NPYR) has been examined in rats and hamsters. Hamster post‐mitochondrial supernatants were able to convert NPYR to a mutagen more efficiently than rat preparations under all conditions studied. Aroclor 1254 pretreatment caused the greatest increase in mutagenic activity in both species while phenobarbital and 3‐methylcholanthrene pretreatment gave intermediate values when compared to uninduced preparations. Microsomal α‐hydroxylation of NPYR was induced by Aroclor 1254 pretreatment in both species. Pretreatment with 3‐methylcholanthrene increased α‐hydroxylation in hamsters but decreased it in rats. Phenobarbital pretreatment only slightly increased microsomal α‐hydroxylation in either species. When microsomal α‐hydroxylation rates were expressed per gram wet weight of liver, better agreement between rates of α‐hydroxylation and mutagenicity in phenobarbital pretreated animals was obtained since inducer associated changes in total microsomal protein content were taken into account. An example of differential induction of an activation pathway (α‐hydroxylation) and a degradative pathway (aldehyde dehydrogenase) is presented to illustrate a potential source of error in the interpretation of metabolic data obtained from post‐microsomal supernatants and whole animal studies.
Sister chromatid exchange induced by short‐lived monoadducts produced by the bifunctional agents mitomycin C and 8‐methoxypsoralen
Authors: Linnainmaa Kaija , Wolff Sheldon 
Published: February 2007

AbstractTo see if DNA crosslinks are involved in the induction of sister chromatid exchange (SCE), Chinese hamster ovary cells were exposed to two bifunctional alkylating agents, mitomycin C and 8‐methoxypsoralen, and their monofunctional derivatives, decarbamoyl mitomycin C and angelicin. The data indicate that monoadducts, rather than crosslinks, are responsible for SCE formation. Furthermore, all agents but angelicin produced short‐lived lesions that led to SCEs in the first period of DNA replication after treatment (twin SCEs), but not in the second (single SCEs). In contrast, angelicin, like methyl methanesulfonate and N‐acetoxyacetylaminofluorene, produced lesions that lasted more than one cycle, indicating that several different types of DNA lesions are capable of SCE induction.
Neuroblast of the grasshopper embryo as a new mutagen test system. Ii. Chromosome breakage induced by in vitro exposure of embryos to the direct‐acting mutagens 4NQO, MNNG, adriamycin, and bleomycin
Authors: Liang Jan C. , Gaulden Mary Esther 
Published: February 2007

AbstractThe dose‐response for the induction of acentric chromosome fragments was determined in neuroblasts of the grasshopper embryo (Chortophaga viridifasciata De Geer, Orthoptera: Acrididae) exposed in vitro to four direct‐acting chemicals known to be mutagenic, clastogenic, and carcinogenic: 4‐nitroquinoline‐1‐oxide (4NQO), N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), Adriamycin (ADM), and bleomycin (BLM). After a 1‐hr exposure followed by a 3‐hr recovery period (untreated cell cycle time is 4 hr), acentric fragments were observed at doses down to 1 μM 4NQO, 1.25 μM M MNNG, and 0.125 μM ADM and BLM. After an 8‐hr continuous exposure, acentric fragments were induced by 4NQO at a dose as low as 0.125 μM. These low concentrations also reduced the number of dividing cells. No chromosome aberrations or mitotic effects were observed in untreated embryos or in those exposed only to the solvent dimethyl sulfoxide.Because of the short cell cycle and the sensitivity of the neuroblast to the induction of acentric chromosome fragments by chemical clastogens, a minimum of time is needed to perform the test. From a comparison with the prominent clastogen test systems currently used, it is concluded that the grasshopper neuroblast test is the fastest and that it detects some agents that some systems do not. Grasshoppers have a worldwide distribution. If neuroblasts of other species prove to be as sensitive to mutagens as those of Chortophaga, investigators in many countries would have available a eukaryotic mutagen test system that is simple, fast, reproducible, and inexpensive.