bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of cytogenetic damage in rodents after short‐term inhalation of benzene
Authors: Erexson Gregory L. , Wilmer James L. , Steinhagen William H. , Kligerman Andrew D. 
Published: February 2007

AbstractExperiments were designed to investigate both the induction of sister chromatid exchanges (SCEs) in peripheral blood lymphocytes (PBLs) and micronuclei (MN) in bone marrow polychromatic erythrocytes (PCEs) of mice and rats after inhalation of benzene (BZ). Male DBA/2 mice (17–19 weeks old) were exposed to target concentrations of either 0, 10, 100, or 1,000 ppm BZ for 6 hr. Male Sprague‐Dawley rats (11–14 weeks old) were exposed to target concentrations of either 0, 0.1, 0.3, 1, 3, 10, or 30 ppm BZ for 6 hr. Blood was obtained by cardiac puncture 18 hr after exposure, and PBLs were cultured in the presence of lipopolysaccharide (mouse B cells, 60 μg/ml) or concanavalin A (rat T cells, 30 μg/ml) to stimulate blastogenesis for SCE analysis. Femoral bone marrow smears from both species were analyzed for MN in PCEs 18 hr after BZ exposure. Mouse PBLs revealed a significant concentration‐related increase in the SCE frequency over controls at 10, 100, or 1,000 ppm BZ. Mouse bone marrow showed a significant concentration‐dependent increase in MN over controls after exposure to 10, 100, or 1,000 ppm BZ. Rat PBLs showed a significant increase in the SCE frequency after exposure to 3, 10, or 30 ppm BZ. The statistical significance of the 1 ppm BZ result was borderline and dependent on the statistical test chosen. Rat cells revealed a significant concentration‐related increase in MN after inhalation of either 1, 3, 10, or 30 ppm BZ. PBLs from treated mice showed significant concentration‐dependent decreases in mitotic indices; however, cell cycle kinetics and leucocyte counts remained unaffected. Rat PBLs showed significant decreases in mitotic activity only after exposure to 3 and 30 ppm BZ, whereas cell cycle kinetics and leucocyte counts were unaffected. These results show that BZ can induce statistically significant cytogenetic effects in PBLs and PCEs of both mice and rats after a 6‐hr inhalation of BZ at low concentrations.
Mutagenicity of fine (< 2.5 μm) airborne particles: Diurnal variation in community air determined by a salmonella micro preincubation (microsuspension) procedure
Authors: Kado Norman Y. , Guirguis Guirguis N. , Flessel C. Peter , Chan Raymond C. , Chang Kuo‐In , Wesolowski Jerome J. 
Published: February 2007

AbstractA simple modification of the Salmonella liquid incubation assay previously developed for detecting mutagens in urine was used to determine mutagenic activity of airborne particulate matter. The modification consists of adding ten times more bacteria (approximately 109 per incubation tube) and five to ten times less metabolic enzymes compared to the plate incorporation method. The mixture volume is approximately 0.2 ml, and the mixture is incubated for 90 min before pouring it according to the standard protocol. The modified procedure (micro preincubation or microsuspension) was approximately ten times more sensitive than the standard plate incorporation test for detecting mutagens in air particulate extracts and approximately ten to 31 times more sensitive for the chemical mutagens 2‐nitrofluorene, 4‐nitroquinoline‐N‐oxide, 2‐aminofluorene, and benzo(a)pyrene in bacterial strain TA98. Mutagenic activity was detected in particle extracts obtained from 1 m3 of air (17 μMg of extract) or less. This microsuspension procedure was applied to air particulate samples collected with low‐volume (15–50 liters per min) virtual‐dichotomous air samplers. Mutagenic activity was associated exclusively with fine particles (aerodynamic diameters of less than 2.5 μm). Diurnal patterns of mutagenic activity (TA98 revertants per cubic meter air) were investigated by measuring filter extracts from 2‐hr samples collected in three San Francisco Bay Area cities during the summer or fall of 1982. Four criteria pollutants—lead, nitrogen dioxide, ozone, and sulfur dioxide—were simultaneously sampled at one location. Mutagenicity from fine particles sampled at this location was highly correlated with lead and much less correlated with nitrogen dioxide, ozone, and sulfur dioxide. The microsuspension procedure is applicable in testing samples of limited mass.
Statistical analyses for in vitro cytogenetic assays using chinese hamster ovary cells
Authors: Margolin B. H. , Resnick M. A. , Rimpo J. Y. , Archer P. , Galloway S. M. , Bloom A. D. , Zeiger E. 
Published: February 2007

AbstractIt is a widely held view that objective statistical criteria are needed for the evaluation of genetic toxicity assays. This paper presents statistical methods for the analysis of data from in vitro sister chromatid exchange (SCE) and chromosome aberration tests that use Chinese hamster ovary cells. For SCEs, an extensive study of solvent control results demonstrated that there is a substantial interday component of variability in the data, and that a Poisson sampling model is applicable to data generated via the protocol of Galloway et al [1985]. Consequently, a trend test for evidence of a dose response is proposed for such SCE data. As an illustration of this statistical method, analysis of data previously considered to be negative [Gulati et al, 1985] indicates that di(2‐ethyl‐hexyl)phthalate induces a weak, but reproducible, SCE dose response in CHO cells. Monte Carlo methods are used to show that the trend test is more sensitive than four other statistical procedures considered for the analysis of Poisson‐distributed SCEs. A similar trend test for dose response in proportions is proposed for chromosome aberration data, where the percent of cells with chromosome aberrations is the response of interest. Sensitivity (or power) studies indicate that three doses and a control with 50 cells/dose point is a reasonable design for an in vitro SCE study that uses the Galloway et al protocol. For in vitro chromosome aberrations, however, three doses and a control with 100 cells/dose point appears to produce too insensitive an assay; an increase to 200 cells/dose point in the Galloway et al protocol seems worthy of serious consideration.
Comparison of multiple parameters of rodent carcinogenicity and in vitro genetic toxicity
Authors: Tennant Raymond W. , Stasiewicz Stanley , Spalding Judson W. 
Published: February 2007

AbstractThe relationship between chemically induced patterns of tumorigenesis in rodents and of in vitro genetic toxicity was evaluated for 73 substances. Tumorigenicity patterns were defined according to sex and species effects, the induction of common or uncommon tumors, and benign or malignant tumors. These results and the genetic toxicity results derived from the testing of chemicals under code were compared. Chemicals that induced tumors in both sexes of both rodent species (trans‐sex/species carcinogens) were divided into those that showed multiple responses in genetic toxicity assays and those that showed little or no response. Some of the nongenotoxic trans‐sex/species carcinogens exhibit properties that do not necessarily fit classification as only tumor promoters and may involve some other mode(s) of action. Those chemicals showing tumorigenicity in only one of the four groups exposed (uni‐sex/species carcinogens) generally showed little or no response in genetic toxicity assays. Uni‐sex/species carcinogens may be difficult to identify by in vitro assays because of their high tissue specificity. Chemicals that are tumorigenic in both sexes of both species are logically more likely to be tumorigenic in a third species than are those that are tumorigenic in only one sex of the exposed species. Therefore, while positive genetic toxicity test results are not predictive of all carcinogens, a consistent positive response among the multiple endpoints in these assays is more likely to identify chemicals with the potential for trans‐sex/species carcinogenesis. Such trans‐sex/species carcinogens may have the most direct implication for human health effects.
Mutagenicity studies in salmonella: Residues of ozonated and/or chlorinated water fulvic acids
Authors: Kowbel David J. , Ramaswamy S. , Malaiyandi M. , Nestmann Earle R. 
Published: February 2007

AbstractAqueous residues of ozonated, chlorinated, and ozonated/chlorinated water fulvic acids (WFA) were tested for induction of His+ reversion in Salmonella typhimurium strain TA100 in fluctuation tests for mutagenicity. The data suggest that ozonation of natural organics present in sources of drinking water can prevent subsequent formation of by‐products of chlorination that are mutagenic in bacteria. Ozonation of the WFA at different pH and at varying dose levels produced residues that were not or were only weakly mutagenic. Chlorination of WFA or of previously ozonated WFA led to residues that were highly mutagenic. However, mutagen formation in the ozonated/chlorinated residues could be prevented, depending upon the pH of the WFA solutions during ozonation—mutagenicity decreased as pH increased. This decrease in mutagenicity is associated with previous observations of enhanced ozone decomposition into its highly reactive oxidant species at higher pH. Since ozonation seems to be more effective at alkaline pH, alkaline raw water sources seem to be the best candidates for water treatment that involves ozonation.
Structure‐activity relationships (SARs) among mutagens and carcinogens: A review
Authors: Frierson Manton R. , Klopman Gilles , Rosenkranz Herbert S. 
Published: February 2007

AbstractThis review is an introduction to methods for evaluating structure‐activity relationships (SARs), and, in particular, to those methods that have been applied to study mutagenicity and carcinogenicity. A brief history and some background material on the earliest attempts to correlate molecular structure and biological activity are included. Most of the discussion focuses on modern methods utilizing extrather‐modynamic and physical property variables such as the Hansch method and SIMCA, and approaches based on molecular connectivity such as the ADAPT, CASE, and Enslein methods. In general, the latter class is potentially the most useful in the study of the large and structurally diverse databases so often encountered in the study of mutagenicity and carcinogenicity. They also are not very sensitive to lab‐to‐lab variances in reported activities and outright misclassifications in activities of some compounds. This is chiefly because the statistical treatments used in these methods tend to dilute the importance of outliers. The methods using physicochemical and extrathermodynamic variables are especially important in relatively small, congeneric databases and can help fine‐tune the role of physicochemical properties in mechanistic hypotheses. All of the above methods have been used to look at mutagenicity and carcinogenicity and some of the results reported in the literature are reviewed here. As far as specific methods go, ADAPT, CASE, SIMCA and the Enslein approach all seem to have similar classification powers (in the range of 75–95%), depending very much on the database studied. The emphasis in this review is on showing that the use of these computer‐aided storage, retrieval and analysis techniques is a timely approach to predicting and even understanding the toxicity of environmental substances. However, each of the methods discussed is still under development, and their potential usefulness for predictive purposes is still being explored.
The use of metabolic inhibitors to compare the excision repair of pyrimidine dimers and nondimer dna damages in human skin fibroblasts exposed to 254‐NM and sunlamp‐produced >310‐NM ultraviolet radiation
Authors: Rosenstein Barry S. , Chao Chuck C.‐K. , Ducore Jonathan M. 
Published: February 2007

AbstractNormal human skin fibroblasts were exposed to either 0–5 J/m2 of 254‐nm ultraviolet (UV) radiation or 0–50 kJ/m2 of the Mylar‐filtered UV (>310 nm) produced by a fluorescent sunlamp. These cells were then incubated for 0–20 min in medium containing 10 mM hydroxyurea (HU) and 0.1 mM 1‐β‐D‐arabinofuranosyl cytosine (ara C), and the yield of DNA strand breaks was measured by means of the alkaline elution technique. For cells irradiated with 254‐nm UV, which results primarily in the formation of cyclobutane pyrimidine dimers, a rapid increase in DNA strand breaks was detected following incubation with these metabolic inhibitors. In contrast, only a low level of strand breaks formed in cells incubated with HU and ara C after irradiation with approximately equitoxic fluences of sunlamp UV >310 nm, which mainly causes the induction of nondimer DNA lesions. Hence, these results are consistent with the conclusion that the pathways involved in the repair of nondimer DNA damages induced by UV wavelengths >310 nm differ from the repair of pyrimidine dimers.
Urine recovery experiments with quercetin and other mutagens using the ames test
Authors: Busch David B. , Hatcher James F. , Bryan George T. 
Published: February 2007

AbstractRecovery from urine of the mutagenic activity of 2‐anthramine, cyclophosphamide, 7,12‐dimethylbenz[a]anthracene, 6‐chloro‐9‐((3‐(2‐chloroethylamino)‐propyl)amino)‐2‐methoxyacridine dihydrochloride (ICR‐191), mitomycin‐C, nitrofurantoin, and quercetin was studied with several of the Ames tester strains using acetone‐extracted XAD‐2 columns with yields ranging from 27% to 79%. Dose responses of the pure chemicals were also studied, and results showed TA 97 to be far more susceptible to quercetin mutagenesis than TA 1537. Reducing pour plate agar volume enhanced mutagenesis.
Formaldehyde‐induced acentric chromosome fragments and chromosome stickiness in Chortophaga neuroblasts
Authors: Dowd Mary Ann , Gaulden Mary Esther , Proctor Bertha L. , Seibert G. Burton 
Published: February 2007

AbstractEmbryos of the grasshopper Chortophaga viridifasciata were exposed in vitro to formaldehyde (FA), as formalin, at concentrations ranging from 10−8 M (0.0003 ppm) to 10−3 M (30 ppm) at 38°C. A low frequency of distinct acentric chromosome fragments (0.02–0.04/cell) was observed in the neuroblasts after 1 hr exposure to 7.5 × 10−4 or 10−3 M FA plus 3 hr recovery, but not at lower concentrations, even with 4 hr exposure. There was no obvious relation between distinct fragment frequency and concentration of FA. Neuroblasts with sticky chromosomes were observed at 10−4, 7.5 × 10−4, and 10−3 M FA, the percent of cells with slight, moderate, or severe stickiness varying with FA concentrations. Fragments were associated with the sticky chromosomes. The frequency of these sticky fragments at the two higher concentrations (0.15–0.30/cell) was greater than the frequency of distinct fragments. It is concluded that the distinct acentric fragments induced by FA result from breakage at a single sticky point (slight stickiness) between separating sister chromatids. The chromosome effects observed probably result from the action of daughter products that are formed by the interaction of FA with culture medium components, especially the fetal calf serum.
Potentiation of sister chromatid exchange by 3‐aminobenzamide is not modulated by topoisomerases or proteases
Authors: Morgan William F. , Doida Yukio , Fero Matthew L. , Xi‐Cang Guo , Shadley Jeff D. 
Published: February 2007

AbstractPoly(ADP‐ribose) is synthesized in response to DNA strand breaks and covalently modifies numerous intracellular proteins. We have proposed that this modification regulates, i.e., inhibits, the activity of these enzymes, e.g., topoisomerases and proteases, which could otherwise cause additional DNA damage or alterations in chromatin structure. Inhibition of poly(ADP‐ribose) polymerase by 3‐amino‐benzamide (3AB) in cells exposed to DNA‐damaging agents would, according to this proposal, eliminate the regulatory role of ADP‐ribosylation. When Chinese hamster ovary cells are cultured with methyl methanesulfonate (MMS) and 3AB, a synergistic increase in sister chromatid exchange frequency is observed. We investigated the regulatory role of poly(ADP‐ribose) polymerase to see if topoisomerases or proteases are involved in this synergistic increase. Cells were exposed to MMS or the intercalating agent 4′‐(9‐acridinylamino)methanesulfon‐m‐anisidide (m‐AMSA), 3AB, and either the topoisomerase inhibitor novobiocin or the protease inhibitor antipain. Neither novobiocin nor antipain affected the synergistic response of MMS and 3AB or the additive response of m‐AMSA and 3AB. These results suggest that topoisomerases or proteases do not account for the effect of 3AB on sister chromatid exchange frequency after DNA damage.
Analysis of the interlaboratory and intralaboratory reproducibility of the enhancement of simian adenovirus SA7 transformation of syrian hamster embryo cells by model carcinogenic and noncarcinogenic compounds
Authors: Schechtman L. M. , Hatch G. G. , Anderson T. M. , Putman D. L. , Kouri R. E. , Cameron J. W. , Nims R. W. , Spalding J. W. , Tennant R. W. , Lubet R. A. 
Published: February 2007

AbstractThe intralaboratory and interlaboratory reproducibility of a DNA virus (SA7) transformation enhancement assay was investigated using nine carcinogenic and noncarcinogenic compounds representing a variety of chemical classes. By the use of standardized procedures designed to limit assay variables, replicate assay data were collected in two independent laboratories and analyzed for concurrence. The carcinogens, 7, 12‐dimethylbenz(a)anthracene, benzo(a)pyrene, and N‐methyl‐N′‐nitro‐N‐nitrosoguanidine yielded reproducible dose‐dependent cytoxicity and positive transformation effects (defined as statistically significant [p ≦ 0.05] enhancement of virus transformation at two or more consecutive dose levels) in all experiments in both laboratories. The carcinogens lead chromate, diethylnitrosamine, 4‐nitroquinoline‐N‐oxide, and 2‐acetylaminofluorene demonstrated enhancement of SA7 transformation at two or more dose levels in 40–50% of the assays. The noncarcinogenic structural analogs anthracene and pyrene consistently did not produce positive assay responses when tested at dose levels up to the limits of solubility. Good interlaboratory concurrence was demonstrated for these model compounds in the Syrian hamster embryo cell‐SA7 assay.
Influence of various parameters on benzo(a)pyrene enhancement of adenovirus SA7 transformation of syrian hamster embryo cells
Authors: Lubet R. A. , Nims R. W. , Kiss E. , Kouri R. E. , Putman D. L. , Schechtman L. M. 
Published: February 2007

AbstractSeveral of the major variable factors in the Syrian hamster embryo/simian adeno‐virus SA7 (SHE/SA7) viral enhancement assay were identified and the effects of these parameters on assay sensitivity were assessed. The extent of dose‐dependent cytotoxicity and enhancement of SA7 transformation of primary SHE target cells by benzo(a)pyrene was examined through analysis of data obtained from 37 assays performed over a 2‐year period. The variables analyzed for contribution to assay sensitivity included (a) the number of SA7‐induced transformed SHE cell foci enumerated in ten replicate dishes in the negative control condition (background focus count) (range: 26–139); (b) the age of the SHE cell cultures at the time of exposure to benzo(a)pyrene (range: 72–144 hr postseeding); and (c) the source of the pregnant hamsters used to prepare the primary SHE cells (Wilmington colony vs Lakeview colony, Charles River Laboratories, Inc., Wilmington, MA). The benzo(a)pyrene‐induced cytotoxicity and enhancement of SA7 transformation responses were found to be independent of each of these variables, within the range of values tested.
Mutagenicity study on pyrazole, seven pyrazole derivatives, and two nitroimidazoles with the L‐arabinose resistance test of Salmonella typhimurium
Authors: Alejandre‐Durán Encarnación , Ruiz‐Rubio Manuel , Claramunt Rosa M. , Lápez Concepción , Pueyo Carmen 
Published: February 2007

AbstractThe mutagenicity of pyrazole and seven pyrazole derivatives (4‐nitropyrazole, 4‐bromopyrazole, 1‐methyl‐4‐nitropyrazole, 3,5‐dimethyl‐4‐nitropyrazole, 1‐methyl‐4‐bromopyrazole, 4,4′‐dinitro‐1, 1′‐methylene‐dipyrazole and 4,4′‐dibromo‐1, 1′‐methylene‐dipyrazole) has been investigated with the L‐arabinose forward mutation assay of Salmonella typhimurium. Two nitroimidazoles (1‐methyl‐5‐nitroimidazole and metronidazole) were included as reference drugs. The mutagenicity of each chemical was determined by both preincubation and liquid tests, in the presence or absence of S9 microsomal fraction. The mutagenic response was expressed as the absolute number of L‐arabinose resistant mutants growing in selective plates, supplemented with traces of D‐glucose. Strain BA13 with a wild‐type lipopolysaccharide barrier was used as a comparison to the deep rough derivative BA9. No mutagenic effect was detected with pyrazole and two of its derivatives, 1‐methyl‐4‐bromopyrazole and 4,4′‐dibromo‐1,1′‐methylene‐dipyrazole. The other five pyrazole derivatives were mutagenic to different degrees, although their mutagenic potencies were always considerably lower than those of the two nitroimidazoles. The results suggest that 4‐nitropyrazoles, as well as 4,4′‐dinitro‐1, 1′‐methylene‐dipyrazoles, should be investigated further as alternatives to, or even substitutes for, the currently used nitroimidazoles.
Bioassay of environmental nickel dusts in a particle feeding ciliate
Authors: Smith‐Sonneborn Joan , Leibovitz Brian , Donathan Robert , Fisher Gerald L. 
Published: February 2007

AbstractThe ciliated protozoan Paramecium was used to quantitate cytotoxic and genotoxic effects of nickel particles. The biological response of these eukaryotic cells to pure nickel powder and iron‐nickel powder was assayed and compared to the effect of the inorganic carcinogen nickel subsulfide. Cytotoxicity was determined by the percent survival of treated cells. Genotoxicity was indicated by significant increases in the fraction of nonviable offspring (presumed index of lethal mutations) found after self‐fertilization (autogamy) in parents from the nickel‐treated versus neutral control groups. The cells were exposed to the dusts and the biological effects determined. Only the nickel subsulfide consistently showed a significant increase in offspring lethality.
Environmental tobacco smoke: Comparative characterization by mutagenicity assays of sidestream and mainstream cigarette smoke
Authors: Löfroth Göran , Lazaridis Georgios 
Published: February 2007

AbstractMainstream cigarette smoke particles were collected by means of a smoking machine, and sidestream particles were collected from the room in which the smoking took place. The particles were extracted by sonication with acetone, and the extracts were solvent‐exchanged to dimethyl sulfoxide. The samples were tested for mutagenicity in the Ames Salmonella/microsome assay. The mainstream extract is preferentially mutagenic in the presence of S9, with about 30,000 revertants/cigarette in TA98, but has little or no activity in its absence. The sidestream extract is also mutagenic in the presence of S9 with TA98, and this activity is mainly due to basic compounds. Sidestream smoke is also significantly mutagenic in the absence of S9 in the strain TA100 as well as in TA97 and TA104. This “direct” activity is due to components that are labile. The response of sidestream particles is 10,000‐20,000 revertants/cigarette in TA98+S9 and TA100‐S9 when the collection is performed in a room where the particle concentration is modulated by deposition to surfaces. Sidestream particles collected on glass fiber filter and by electrostatic precipitation (ESP) with a commercial air cleaning device gave essentially the same mutagenic response, showing that ESP sampling may be an alternative to filter sampling for environmental tobacco smoke (ETS) in indoor environments. ESP sampling in children's rooms in smoking and nonsmoking homes showed that 5–10% of the tobacco smoke emitted in the smoking homes entered the child's room, demonstrating that diffusion of pollutants is faster than ventilation in modern buildings with low ventilation rates.