bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selenium‐mediated reduction in the mutagenicity of cigarette smoke
Authors: Chortyk O. T. , Baker J. L. , Chamberlain W. J. 
Published: February 2007

AbstractCigarette smoke contains carcinogens and mutagens and affects the health of smokers. Recently, increased research has proven the potentially protective activity of selenium (Se) against heavy metal toxicity, cancer, and other health disorders. Accordingly, we have proposed the fortification of tobacco with Se to develop safer cigarettes. As a start in evaluating any biological effects of added Se, we have determined the mutagenicity of inhaled, mainstream (MS) cigarette smoke condensate (CSC), with and without Se, in the preincubation assay of the Ames test. Initially, it was shown that Se, as sodium selenite, was not mutagenic at high concentrations (up to 80 μg/plate) with strains TA1538 and TA1978. Subsequently, the effects of different levels of Se, added to MS CSC, were examined with TA98, TA100, and TA1538. On the average, addition of 10 μg Se produced mutagenicity reductions of about 50%. Higher levels of added Se yielded further reductions. Cigarette sidestream (SS) smoke, collected between puffs, was also tested. Again, Se added to SS‐CSC gave similar reductions, confirming its antimutagenic effect for both mainstream and sidestream smoke.
Inhibition of aminoimidazoquinoxaline‐type and aminoimidazol‐4‐one type mutagen formation in liquid‐reflux models by the amino acids L‐proline and/or L‐tryptophan
Authors: Jones R. Conrad , Weisburger John H. 
Published: February 2007

AbstractLaboratory models were used to study the inhibition of mutagen formation by Maillard‐type reactions during cooking of meats or fish. The amino acid L‐proline (L‐pro) was an effective, dose‐dependent inhibitor of the development of mutagenicity (Ames test) in a liquid‐reflux model of glucose + glycine + creatinine known to produce IQ‐type mutagens (MeIQx and 7,8‐DiMeIQx). L‐pro also inhibited formation of mutagens in a reflux model of threonine + creatinine, developed in our laboratory, which yields a novel class of IQ‐“like” aminoimidazol‐4‐one mutagens. A mixture of L‐pro and L‐tryptophan (L‐trp) at lower concentrations of each yielded increased inhibition, compared with the findings when each inhibitor was tested by itself.
In vivo evaluation of the genotoxic potential of curacron in somatic cells of mice
Authors: Nahas Soheir M. El , De Hondt H. A. , Ramadan Hassan A. I. 
Published: February 2007

AbstractCytogenetic effects produced in somatic cells by Curacron, a phosphoric acid ester insecticide, were assessed in mice by three criteria: chromosome aberrations, sister chromatid exchange (SCE), and micronucleus induction. Curacron significantly increased the frequency of all three in an apparent dose‐dependent manner. Curacron also inhibited the mitotic activity. The increased number of micronuclei is comparable to the increase in chromosome aberrations; the latter were mainly breaks. The frequency of SCE was considerably less than the frequencies of micronuclei and chromosome aberrations.
Identification of aneuploidy‐inducing agents using cytokinesis‐blocked human lymphocytes and an antikinetochore antibody
Authors: Eastmond David A. , Tucker James D. 
Published: February 2007

AbstractThe identification of agents causing aneuploidy in humans, a condition associated with carcinogenesis and birth defects, is currently limited due to the highly skilled and time‐consuming nature of cytogenetic analyses. We report the development of a new simple and rapid assay to identify aneuploidy‐inducing agents (aneuploidogens). The assay involves the chemical‐ or radiation‐induced formation of micronuclei in cytokinesis‐blocked human lymphocytes and the use of an antikinetochore antibody to determine whether the micronuclei contain centromeres—a condition indicating a high potential for aneuploidy. All agents tested produced dose‐related increases in the frequency of micronucleated cells. The micronucleated cells induced by the known aneuploidogens—colchicine, vincristine sulfate, and diethylstilbestrol—contained kinetochore‐positive micronuclei 92, 87, and 76% of the time, respectively. In contrast, the micronucleated cells induced by the potent clastogens—ionizing radiation and sodium arsenite—contained kinetochore‐positive micronuclei only 3 and 19% of the time, respectively. These results indicate that this relatively simple assay can discriminate between aneuploidogens and clastogens and may allow a more rapid identification of environmental and therapeutic agents with aneuploidy‐inducing potential.
Role of oxygen free radicals in the induction of sister chromatid exchanges by cigarette smoke
Authors: Lee Chin K. , Brown Buddy G. , Rice William Y. , Doolittle David J. 
Published: February 2007

AbstractCigarette smoke has been reported to contain free radicals and free radical generators in both the gas and particulate phases. Studies in our laboratory have shown that both cigarette smoke condensate (CSC) and smoke bubbled through phosphate buffered saline solution (smoke‐PBS) increased sister chromatid exchanges (SCE) in Chinese hamster ovary cells in a dose‐dependent manner. Since oxygen free radicals have been shown to cause SCEs and other chromosomal damage, we investigated the role of these radicals in the induction of SCEs by CSC and smoke‐PBS. Addition of the antioxidant enzymes catalase and superoxide dismutase or the oxygen‐radical scavenger ascorbic acid failed to reduce the SCE frequency in the presence of either CSC or smoke‐PBS. Additional studies indicated that the quantity of hydrogen peroxide produced in CSC or smoke‐PBS is too small to account for the observed SCE induction. It appears, therefore, that SCE induction by CSC or smoke‐PBS does not involve the participation of oxygen free radicals.
Testing of sunset yellow and orange II for genotoxicity in different laboratory animal species
Authors: Wever J. , Münzner R. , Renner H. W. 
Published: February 2007

AbstractThe azo dyes Sunset Yellow and Orange II were gavaged to rodent species to check bile, urine, and fecal extracts for possible mutagenic activity in the Ames test or in bone marrow cells for clastogenicity using cytogenetic test systems. After oral application the dyes showed a negative response in bile, excrements, and bone marrow. When an exogenous metabolic activation was performed, increased revertant numbers using Salmonella strain TA100 were obtained only in fecal extracts of Sunset Yellow‐treated animals. It is concluded that no genotoxic harm is to be expected from the ingestion of Sunset Yellow or Orange II.
Application of the carcinogenicity prediction and battery selection method to recent national toxicology program short‐term test data
Authors: Ennever Fanny K. , Rosenkranz Herbert S. 
Published: February 2007

AbstractIdentification of potentially cancer‐causing chemicals is a priority in our society. Short‐term assays for mutation or chromosomal damage, which are rapid, inexpensive, and reproducible, have found widespread use; however, concern has arisen recently because such assays do not coincide completely with the standard rodent bioassay for carcinogenesis. Lack of perfect correlation is not surprising, given the complex, multicausal nature of the carcinogenic process. We have developed methodologies for interpreting short‐term tests to predict carcinogenicity, which allow consideration of the influence of the proportion of carcinogens expected in the tested chemicals, the complexities of the rodent carcinogenesis bioassay, and factors affecting the worth of information. These methodologies are applied to a set of data on genotoxicity and carcinogenicity of 73 chemicals (NTP‐73) recently published by the National Toxicology Program; they illustrate that with this approach, batteries of short‐term tests can indeed be predictive of rodent carcinogenicity or noncarcinogenicity and that batteries are more predictive than the Salmonella assay alone. The analysis is validated using an additional group of chemicals with results in the same short‐term tests as NTP‐73.
Results of tests for micronuclei and chromosomal aberrations in mouse bone marrow cells with the human carcinogens 4‐aminobiphenyl, treosulphan, and melphalan
Authors: Shelby Michael D. , Gulati D. K. , Tice Raymond R. , Wojciechowski J. P. 
Published: February 2007

AbstractThree human carcinogens, 4‐aminobiphenyl, treosulphan, and melphalan, were tested for the induction of micronuclei or chromosomal aberrations in the bone marrow cells of male B6C3F1 mice. These studies were conducted to provide further information on the in vivo genetic toxicity of compounds known to cause cancer in humans. All three compounds gave positive results in the mouse bone marrow micronucleus test, and melphalan, the only compound tested for aberration induction, was positive in this assay. These results extend the evidence that nearly all known human carcinogens are detected in relatively simple and widely employed short‐term in vivo tests.
Evaluation of a rat tracheal epithelial cell culture assay system to identify respiratory carcinogens
Authors: Steele Vernon E. , Arnold Julia T. , Van Arnold John , Mass Marc J. 
Published: February 2007

AbstractTo evaluate a short‐term epithelial cell assay system to detect respiratory carcinogens, primary cultures of rat tracheal epithelial cells were exposed to a series of 17 compounds and scored for morphologically transformed cell colonies 28 days later. The test compounds included known carcinogens and noncarcinogens in volatile or liquids form. Tracheal epithelial cells were isolated from F344 rats, plated onto collagen‐coated dishes, and exposed to the test compounds on day 1 for 24 hours. At day 30 the cultures were fixed, stained, and scored for colonies having a density greater than 1,300 cells/mm2. With standardized protocols, such colonies are very infrequent in media and sol‐vent control cultures. Concentration levels for each chemical were chosen over a range from nontoxic to toxic levels. Highly positive compounds in this assay included benzo(a)pyrene, benzo(l)acean‐thrylene, 3‐methylcholanthrene, and formaldehyde. Compounds which were negative in this assay included pyrene, benzo(e)pyrene, and 4‐nitroquinoline‐N‐oxide. Examining the concordance of in vitro results with whole animal car‐cinogenesis studies revealed an accuracy of 88% with one false‐positive and one false‐negative compound. The results of these studies indicate that the rat tracheal epithelial cell assay may be useful in identifying potential respiratory carcinogens in our environment.
Morphological and neoplastic transformation of C3H/10T1/2 Cl 8 mouse embryo cells by insoluble carcinogenic nickel compounds
Authors: Miura Takeshi , Patierno Steven R. , Sakuramoto Toshio , Landolph Joseph R. 
Published: February 2007

AbstractWe studied induction of cytotoxicity and morphological transformation in C3H/10T1/2 Cl 8 (10T1/2) mouse embryo fibroblasts by soluble and insoluble carcinogenic nickel compounds. Soluble nickel sulfate and nickel chloride caused dose‐dependent cytotoxicity in the concentration range from 0.5 μM to 100 μM after 48 hr treatments, but neither compound induced morphological transformation even at concentrations causing up to 94% cytotoxicity. Insoluble nickel subsulfide, nickel monosulfide, and nickel oxide caused dose‐dependent cytotoxicity and a low, dose‐dependent frequency of morphological transformation in the concentration ranges from 0.5 to 40 μM, 5 to 50 μM, and 50 to 400 μM, respectively, after 48 hr exposure of cells to these compounds. Foci were predominantly of type II morphology; type III foci were rare. The insoluble nickel compounds studied caused no induction of base substitution mutations to ouabain resistance in 10T1/2 cells over concentration ranges that induced morphological transformation. Nickel subsulfide and nickel monosulfide were taken into cells by phagocytosis, since particles were visible in intracytoplasmic vacuoles. Numerous nickel oxide particles were found associated with cells, but true phagocytic uptake was difficult to detect since no vacuoles were observed. We twice cloned type II and type III foci induced by insoluble nickel compounds, established independent cell lines, and characterized their phenotypes. Four of seven of these cell lines had three‐ to fourfold increased saturation densities compared to 10T1/2 cells, formed type II and type III foci in reconstruction assays, and grew in soft agarose. One cell line induced by nickel oxide formed tumors in nude mice. These data indicate that insoluble carcinogenic nickel compounds induced type II foci in 10T1/2 cells, some of which were tumorigenic, and that the 10T1/2 cell system is suitable for studying mechanisms of nickel compound‐induced morphological transformation in mammalian cells.
Intralitter variation in murine fetal sister chromatid exchange responses to the transplacental carcinogen ethyl carbamate
Authors: Neeper‐Bradley T. L. , Conner Mary K. 
Published: February 2007

AbstractGravid Swiss Webster dams were injected via tail vein with a single (1.1, 2.2, or 3.3 mmol/kg) dose of ethyl carbamate (urethane) on days 13–17 of pregnancy. Relative sister chromatid exchange (SCE) responses in maternal bone marrow vs. individual fetal liver cells were assessed. In addition, in order to evaluate the significance of intralitter variability in fetal SCE responses, SCE in combined (“pooled”) fetal liver tissue preparations were measured and compared with average individual responses. In contrast to maternal responses, average fetal SCE responses to ethyl carbamate varied with gestational age. In addition, significant variation was observed among individual littermate responses at all dose levels. Nonetheless, fetal SCE responses determined from “pooled” tissue preparations provided a valid estimate of average litter responses. Regardless of the method of SCE evaluation in fetal tissue or gestational age, maternal bone marrow exhibited greater sensitivity than fetal liver to SCE induction by ethyl carbamate.
Lack of genotoxicity with acrylate polymers in five short‐term mutagenicity assays
Authors: Thompson E. D. , Aardema M. J. , Leboeuf R. A. 
Published: February 2007

AbstractTwo linear polymers of acrylic acid (average molecular weight = 2,000 and 4,500) and one linear copolymer of acrylic and maleic acids (average molecular weight = 12,000) were tested for mutagenicity with the Salmonella mammalian microsome assay, the L5178Y mouse lymphoma assay at the TK locus, an unscheduled DMA synthesis assay in primary cultures of rat hepatocytes, and either an in vitro cytogenetic assay with CHO cells or the bone marrow micronucleus assay in mice. The results of all the assays were uniformly negative for the three polymers.
5‐azacytidine induces sex chromosome loss and interchange in immature germ cells of Drosophila mei‐9 males
Authors: Osgood Christopher J. , Seward Sonya M. 
Published: February 2007

Abstract5‐Azacytidine (5‐AZ) profoundly affects gene expression and chromosome structure in higher eukaryotes, presumably by disrupting normal patterns of DNA methylation. The DNA of several eukaryotic species, including Drosophila melanogaster, is virtually devoid of 5‐methylcytosine, and the spectrum of mutagenic effects induced by 5‐AZ in such organisms is less well characterized. To investigate the mutagenicity of 5‐AZ in Drosophila germ cells, DNA repair‐deficient (mei‐9) Drosophila 72‐hr‐old larvae were fed on medium containing 5‐AZ, and recovered adult males were tested for induced losses and interchanges involving the paternal sex chromosomes. Moderately toxic doses of 5‐AZ were found to induce significant rates of apparent complete losses (CL) of the paternal sex chromosomes, partial losses (PL) of one of the arms of‐the submetacentric Y‐chromosome, and interchanges (X‐Y) between the X‐chromosome and the short arm of the Y‐chromosome. The data suggest that, of the stages tested, germ cells in the early primary spermatocyte stage of development are maximally sensitive to 5‐AZ‐induced sex chromosome loss and rearrangement. X‐Y interchanges comprised a substantial fraction of the 5‐AZ‐induced breakage events involving the Y‐chromosome; in contrast with classical clastogens such as X‐rays, the pattern of interchange products suggests that 5‐AZ acts by enhancing the frequency of pairing‐dependent interchanges between the paternal sex chromosomes.
Mutagenesis and mathematics: The allure of numbers
Authors: Haynes Robert H. 
Published: February 2007

AbstractThis paper sets out the “formal,” “empirical,” and “mechanistic” equations that my colleagues and I have developed for the description and analysis of dose‐response data on the lethal and genetic effects of mutagens in microorganisms. These three types of equations are interrelated inasmuch as they are all based ultimately on the use of the Poisson distribution in the formal definition of lethal and mutational hit functions. Explicit mathematical expressions for these functions can be written down in either empirical or mechanistic terms. The empirical equations are obtained simply by writing the hit functions as finite polynomials with adjustable coefficients. The mechanistic equations are based on the assumptions of the “DNA damage‐repair hypothesis.” The mathematical formulation of this hypothesis entails an important change in the definition of the word “hit” from that used in the classical hit/target theory of radiation biology. The theoretical and practical applications of these various equations in mutation research are summarized briefly and their merits are assessed in light of recent advances in our understanding of the biochemical basis of mutagenesis.
Assays of three carcinogen/non‐carcinogen chemical pairs for in vivo induction of chromosome aberrations, sister chromatid exchanges and micronuclei
Authors: McFee Alfred F. , Jauhar Prem P. , Lowe Karen W. , Macgregor James T. , Wehr Carol M. 
Published: February 2007

AbstractThree pairs of structurally similar carcinogenic/ non‐carcinogenic chemicals were tested for in vivo genotoxic activity in B6C3F1 mice. The carcinogenic/non‐carcinogenic pairs, respectively, were o‐toluidine hydrochloride/o‐anthranilic acid, 4‐chloro‐o‐phenylenediamine/4‐nitro‐o‐phenylenediamine, and 3‐(chloromethyl)pyridine hydrochloride/2‐(chloromethyl)pyridine hydrochloride. Bone marrow cells from mice given intraperitoneal injections of up to the maximum tolerated dose were evaluated for chromosomal aberration, sister chromatid exchange, and micronucleus induction, o‐anthranilic acid and o‐toluidine hydrochloride did not increase the frequency of chromosomal aberrations or micronuclei. o‐Toluidine hydrochloride increased the frequency of sister chromatid exchanges in two successive trials, while o‐anthranilic acid had a positive effect on sister chromatid exchanges in two of three trials. Both 2‐(chloromethyl) and 3‐(chloromethyl)pyridine hydrochloride were negative for all three endpoints. Assays for chromosomal aberrations and micronuclei each distinguished between 4‐chloro‐o‐phenylenedi‐amine and its non‐carcinogenic companion, 4‐nitro‐o‐phenylenediamine. In the aberration test, 4‐chloro‐o‐phenylenediamine produced a few cells with very large numbers of aberrations rather than an even distribution of damage among cells.
Effects of human placental S9 and induced rat liver S9 on the mutagenicity of drinking waters processed from humus‐rich surface waters
Authors: Vartiainen T. , Lampelo S. 
Published: February 2007

AbstractThe mutagenicity of chlorinated drinking waters processed from humus‐rich surface waters has been shown to be very high. The effect of placental S9 on the mutagenicity of drinking waters has not been studied previously. The purpose of this study was to compare the effects of human placental and rat liver microsomal fractions on the mutagenicity of drinking waters processed from humus‐rich surface waters. The samples of 34 drinking and two raw waters from 26 localities in Finland were tested for mutagenicity in Ames Salmonella typhimurium tester strain TA100 with and without metabolic activations. Between the drinking water samples, clear differences were recorded in the presence of placental and rat liver S9, suggesting different mutagens in the drinking waters. Rat liver S9 decreased the mutagenicities of drinking water concentrates, but placental S9 increased, decreased, or had no effect. It is not known if placental mutagenicity enhancing system might cause any health hazard to a developing fetus.
A concerted approach to the study of the aneuploidogenic properties of two chelating agents (EDTA and NTA) in the germ and somatic cell lines of Drosophila and the mouse
Authors: Zordan M. , Russo A. , Costa R. , Bianco N. , Beltrame C. , Levis A. G. 
Published: February 2007

AbstractThe genetic effects of nitrilotriacetic acid (NTA) and ethylenedinitrilotetraacetic acid (EDTA), two widely used chelating agents, were investigated by using a somatic mutation and recombination test (SMART) after treatment of larvae and the FIX test for aneuploidy after treatment of adult female Drosophila melanogaster. Chloral hydrate (CH) and 5‐fluorodeoxyuridine (FdUr) were used as positive controls. Effectively absorbed amounts of the test compounds assayed in Drosophila were estimated at the single fly level by a method using 3H‐leucine. NTA and EDTA were also assayed in tests for aneuploidy based on chromosome counting in mouse germ and somatic cells. We previously showed that NTA was able to induce aneuploidy (chromosomal gain) in the germ cells of both Drosophila and the mouse when tested at the exposure levels of 5 × 10−2 M and 275 mg per kg body weight, respectively Costa et al., Environ Mol Mutagen 12:397‐407, 1988). In the present experiments, EDTA was assayed at 2.5 × 10−2 M and 7.5 × 10−3 M in the FIX test adopting a three‐stage brooding scheme. Significant increases (with respect to controls) in chromosomal loss were observed in the second brood and in the combined three‐brood total for both exposure levels of EDTA. In the SMART test, treatments with EDTA in the same exposure range produced negative results over all end‐points, whereas significant increases in the frequency of small single spots (possibly due to aneuploidy) were produced by NTA 5 × 10−2 M. In the cytogenetic assays for aneuploidy both in the germ and somatic cells of the mouse, negative results were also obtained following the i.p. administration of 93 and 186 mg EDTA per kg b.w. The previously observed induction of germ cell aneuploidy by NTA (275 mg per kg b.w.) was confirmed in the present experiments on a different strain of mice. NTA (138‐275 mg per kg b.w.) did not induce aneuploidy in somatic cells of the mouse Russo et al., Mutat Res 226: 111‐114, 1989, however. These results are compared and discussed with reference to the characteristics of the different test systems used and to the different chelating properties of NTA and EDTA.
Observation of frequencies of lymphocytes with micronuclei in human peripheral blood cultures from workers in a sulphuric acid factory
Authors: Meng Ziqiang , Zhang Lianzhen 
Published: February 2007

AbstractFrequencies of lymphocytes with micronuclei (MNF) in human peripheral blood cultures from workers in a sulphuric acid factory (the SO2 concentrations in the workplace ranged from 0.34 mg/m3 to 11.97 mg/m3 air) were investigated. It was shown that among 40 workers, the MNF of 28 workers was more than 0.1 %, and the MNF of 7 workers was greater than the upper limit of the normal range (0.2%). The mean MNF of the worker and the control group was 0.168% and 0.071%, respectively. The difference between them was statistically significant (P < 0.001). It implies that SO2 is a clastogenic and genotoxic agent. No positive correlation between the MNF and length of service in workers has been observed. In the control population, the MNF of smokers was significantly higher than that of non‐smokers (P < 0.001).