bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome aberrations in mouse bone marrow cells following treatment in vivo with vinblastine and colcemid
Authors: Satya‐Prakash K. L. , Liang Jan C. , Hsu T. C. , Johnston Dennis A. 
Published: February 2007

AbstractThe present study was undertaken to determine if chemicals that are capable of inducing mitotic arrest and aneuploidy can also induce chromosomal breakage. Two chemicals, vinblastine and Colcemid, were selected to be studied. Their potentially clastogenic effects were investigated in mouse bone marrow cells in vivo. Two doses of vinblastine, 10−5 M (9 mg/kg) and 10−6 M (0.9 mg/kg), and one dose of Colcemid 10−4 M (37 mg/kg), were administered to mice as single intraperitoneal injections. Bone marrow preparations were made at multiple time periods after injections, ie, 17, 24, 48, 72, and 96 hr. Both these agents, at the concentrations tested, induced mitotic arrest of bone marrow cells within 5 hr after injection. In recovering bone marrow cell populations, 2–3 days after drug administration, significantly elevated levels of chromosomal breakage (mainly the chromatid type) were observed. Vinblastine was found to be much more potent than Colcemid. Since both of these agents affect mainly microtubules, their actions to cause chromosomal breakage are likely to be indirect. Several possible clastogenic mechanisms such as interference with DNA synthesis, active metabolites, and cytoplasmic endonucleases are discussed.
Tests for mutagenic effects of ammoniated glycyrrhizin, butylated hydroxytoluene, and gum arabic in rodent germ cells
Authors: Sheu C. W. , Cain K. T. , Rushbrook C. J. , Jorgenson T. A. , Generoso W. M. 
Published: February 2007

AbstractAmmoniated glycyrrhizin, butylated hydroxytoluene, and gum Arabic are “generally recognized as safe” (GRAS) substances that are used primarily as additives in foods. These substances were incorporated into rodent diets and fed to male rats and mice for 10 and 8 wk, respectively. The treated male mice and rats were then tested for dominant lethal effects. The mice were also tested for induced heritable translocation. Results of the rat studies indicated a statistically significant dominant lethal effect of each of the compounds tested; however, the biological significance of this response is not known. Results of the mouse dominant lethal and heritable translocation studies, on the other hand, indicated no adverse effects of the compounds tested.
In vitro induction of sister chromatid exchanges and chromosomal aberrations in peripheral lymphocytes of the oyster toadfish and american eel
Authors: Ellingham Tara J. , Christensen Elizabeth A. , Maddock Michael B. 
Published: February 2007

AbstractA series of experiments was conducted to characterize the proliferation of oyster toadfish lymphocytes in medium containing 5‐bromodeoxyuridine (BrdUrd) and to determine the effectiveness of cytogenetic endpoints for assessing the genotoxic effects of in vitro exposure of toadfish and eel lymphocytes to known mammalian clastogens. Although the rate of proliferation of toadfish lymphocytes was low compared to that of mammalian lymphocytes, the effects of increasing BrdUrd concentrations were similar, in that proliferation exhibited a concentration‐dependent inhibition for concentrations above 10 μM BrdUrd, and sister chromatid exchange (SCE) frequencies exhibited a concentration‐dependent increase for concentrations above 100 μM BrdUrd. Mitomycin C (MMC) and ethylene dibromide (EDB) induced concentration‐dependent increases in chromatid‐type exchange and SCE frequencies with least effective concentrations (control SCE frequency divided by the slope of the least‐squares line) for SCE induction by MMC (6.8 × 10−9 M) and EDB (2.6 × 10−4 M) that were comparable to or slightly lower than those that have been obtained with mammalian in vitro systems. In vitro exposure of toadfish lymphocytes to dimethoate (DIM) induced a concentration‐dependent increase in SCE frequency with a least effective concentration of 2.8 × 10−3 M that was much higher than that observed with mammalian in vitro systems. In vitro exposure of American eel lymphocytes to MMC also induced a concentration‐dependent increase in the frequency of chromosomal aberrations and SCEs with a least effective concentration for SCE induction of 2.0 × 10−9 M. These results indicate that cytogenetic endpoints can be effectively scored with cultured lymphocytes from these and perhaps other fish species with comparable karyotypes that contain an average of at least 0.07 pg DNA/chromosome.
Induction of SOS genes of Escherichia coli by chromium compounds
Authors: Llagostera Montserrat , Garrido Salvador , Guerrero Ricardo , Barbé Jordi 
Published: February 2007

AbstractThe induction of several SOS genes of Escherichia coli such as recA, umuC, and sfiA by hexavalent (K2Cr2O7, K2CrO4, and CrO3) and trivalent (CrCl3, Cr(NO3)3, and (CH3COO)3Cr) compounds of chromium was studied. Induction was measured as β‐galactosidase activity, using lacZ gene fusions under the control region of different SOS genes. The hexavalent chromium forms induced the genes responsible for massive synthesis of RecA protein, error‐prone repair, and inhibition of cell division. On the other hand, the trivalent chromium compounds were unable to induce any of the SOS genes tested. Individual assay of hexavalent chromium compounds showed that K2Cr2O7 was a stronger inducing agent of those three SOS genes tested than K2CrO4, which, in turn, was stronger than CrO3. All this data led to the conclusion that hexavalent chromium compounds, but not trivalent, are proficient agents of induction of the SOS system and can produce indirect mutagenesis in Escherichia coli.
Induction of sister chromatid exchanges in murine colonic tissue
Authors: Couch David B. , Gingerich John D. , Stuart Earl , Heddle John A. 
Published: February 2007

AbstractAs cancers of the large bowel arise primarily in the epithelial cells of the colon, measurement of genetic damage induced in those cells may aid in elucidating contributing factors in the etiology of the disease. Accordingly, procedures for the in vivo measurement of sister chromatid exchanges (SCE) have been adapted for use with colonic cells. Agar‐coated 5‐bromo‐2′‐deoxyuridine (BrdUrd) tablets were implanted (s.c.) in mice and colonic tissue prepared for measurement of SCE 48 hr later. When mice were treated by intraperitoneal injection with 20 mg/kg 1,2‐dimethylhydrazine (DMH), a colon carcinogen, a significant increase over control SCE frequencies was found when treatment with carcinogen occurred in the interval from 14 hr before to 36 hr following BrdUrd administration. Treatment with DMH 2 hr following implantation of BrdUrd produced a dose‐dependent increase in SCE frequencies, with the highest dose (20 mg/kg) resulting in frequencies approximately twice those of controls. Dimethylhydrazine was not found to be effective in inducing SCE in bone marrow cells of mice. As SCE can be induced by carcinogens and mutagens, measurement of SCE in colonic epithelium may be useful in identifying potential colon carcinogens.
A review of the symposium on aneuploidy: Etiology and mechanisms
Authors: Hoffmann George R. , Dellarco Vicki L. , Voytek Peter E. 
Published: February 2007

AbstractA symposium titled “Aneuploidy: Etiology and Mechanisms” was held in Washington, D.C., in March, 1985. The stimulus for convening it was the growing concern that environmental agents with the capacity to induce aneuploidy can have detrimental effects on human health. Major components of the symposium were devoted to an analysis of human aneuploidy, mechanisms by which aneuploidy originates, and tests for the detection of agents that induce aneuploidy. This review outlines the content of the symposium, its conclusions, and major uncertainties in the field.
Glutathione: A protective agent in Salmonella typhimurium and Escherichia coli as measured by mutagenicity and by growth delay assays
Authors: Owensm Roland A. , Hartman Philip E. 
Published: February 2007

AbstractCultures of some aerobically grown strains of Salmonella typhimurium and Escherichia coli contain up to 24 μM extracellular glutathione (GSH) [Owens RO, Hartman PE (1985): Environ Mutagen 7(Suppl 3): 47] in addition to having intracellular GSH concentrations in the millimolar range. The addition of 26 μM GSH to cultures of Salmonella typhimurium strain TA1534 partially protected the bacteria from the toxic effects causing growth delay by 54 μM N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG). When MNNG was preincubated with equimolar GSH, the mutagenicity of the MNNG was neutralized. The addition of micromolar GSH to cultures of an Escherichia coli GSH− strain protected the cells from growth inhibition by micromolar concentrations of mercuric chloride, methyl mercuric chloride, silver nitrate, cisplatin, cadmium chloride, cadmium sulfate, and iodoacetamide. In the cases of mercuric chloride, cisplatin, MNNG, silver nitrate, and iodoacetamide, reaction products with GSH were detected by paper chromatography. In contrast to reduced GSH, micromolar concentrations of oxidized glutathione (GSSG) provided little or no protection and formed no detectable reaction products. Export of GSH by enteric bacteria may provide an important defense mechanism against exogenous toxic agents otherwise active in the micromolar range.
Genetic and physiological modulation of anthracycline‐induced mutagenesis in Salmonella typhimurium
Authors: Cebula Thomas A. 
Published: February 2007

AbstractThe genotoxic properties of adriamycin and daunomycin, anthracycline antibiotics effective in the treatment of a wide variety of malignancies, were examined in the Salmonella/Ames reverse‐mutation test. A novel time‐ and temperature‐dependent phenomenon that potentiates the mutagenicity of these compounds, termed mutational enhancement, is described. The results of congeneric and chemical attenuation studies imply that anthracycline‐induced free radicals contribute substantively to the mutagenic potentials of adriamycin and daunomycin. These studies show that adriamycin and daunomycin are not simple intercalative compounds. Rather, anthracycline‐induced mutagenesis entails at least two separate but intimately related steps, namely, intercalation within discrete base sequences and the free‐radical‐mediated events that ensue. Implications of the nonrandom and site‐specific action of the anthracyclines are discussed.
Comparison of in vivo and in vitro cytogenetic assay results
Authors: Thompson Edward D. 
Published: February 2007

AbstractIn vitro mutagenicity assays have largely replaced whole animal studies for screening compounds for genotoxic potential. While numerous comparisons have been made between the results of these assays and cancer assays in rodents, comparisons between in vitro and in vivo mutagenicity studies where the genetic endpoints are the same have not been published. To this extent, the published literature was reviewed for chemicals that had been tested in both in vitro and in vivo cytogenetic assays. Two hundred sixteen chemicals were identified, and definitive test results were obtained for 181 of them. Results from the two assays agreed on 126 of the compounds and of the 55 compounds for which the results did not agree, 53 were positive in vitro and negative in vivo. The proportion of “false positives” and the significance of the two “false negatives” are discussed.
Mutational specificity of animal cell DNA polymerases
Authors: Roberts John D. , Kunkel Thomas A. 
Published: February 2007

AbstractSince DNA polymerases are involved in DNA replication, recombination, and repair, the frequency with which these enzymes commit errors during synthesis is likely to be an important factor in controlling mutation rates in cells. The fidelity of DNA polymerases was originally studied by following misincorporation using synthetic nucleic acid templates containing only one or two bases. Later, by assaying for reversion of an amber codon after copying φX174 single‐stranded DNA molecules, the base substitution accuracy of in vitro DNA synthesis on natural DNA was determined. Most recently, a forward mutation assay has been developed that uses gap‐filling synthesis on an M13mp2 DNA template, thus permitting the detection of a variety of different errors during DNA synthesis on natural DNA templates. Detailed mutational spectra for animal cell polymerases‐α, β, and γ have been determined and demonstrate that a variety of errors can be generated by these purified enzymes.The frequencies of base mispairs, base additions, and deletion errors by DNA polymerases vary widely and depend on both the DNA sequence and the enzyme used. An understanding of the mechanisms by which DNA polymerases avoid or generate various mutations depends on the definition of the parameters that influence the frequency and specificity of particular errors. Future experiments will combine the use of the methods available to measure fidelity with advances in DNA replication enzymology and should lead to exciting new insights into the mechanisms of spontaneous mutagenesis.
Short‐term test results for NTP noncarcinogens: An alternate, more predictive battery
Authors: Ennever Fanny K. , Rosenkranz Herbert S. 
Published: February 2007

AbstractA battery of short‐term tests used to predict whether or not a chemical is a carcinogen must be both sensitive (correctly identifying carcinogens) and specific (correctly identifying noncarcinogens). A recent publication [Shelby and Stasiewicz, 1984, Environ Mutagen 6:871–876] of results in four short‐term tests for 70 noncarcinogens tested under the aegis of the National Toxicology Program (NTP) indicates that the battery of short‐term tests lacked specificity. We have analyzed these results using the Carcinogen Prediction and Battery Selection (CPBS) procedure and calculated that the specificity of the NTP battery is indeed very low, i.e., 0.50. Using published data from NTP, the GeneTox program of EPA, and the collaborative study of the WHO International Programme on Chemical Safety, we have constructed an alternate battery that has fewer false positives; this battery has a specificity of 0.80. Thus, the lack of specificity of the original NTP battery does not imply that no set of short‐term tests is able to predict carcinogenicity accurately.
Inactivity of glycerol formal in a mouse micronucleus assay: Relationship to its teratogenicity
Authors: Ashby J. , Ratpan Flora 
Published: February 2007

AbstractGlycerol formal (GF) has been reported to be teratogenic to the rat. Its mechanism of action in this respect has not been defined, but it has been discussed within the context of its being a possible slow formaldehyde‐releasing agent. In order to evaluate this possibility, the hydrolysis of GF has been studied, and its activity as a mouse bone marrow clastogen assessed using the micronucleus assay. Neither was hydrolysis observed, nor was the test agent active as a clastogen in vivo. It is therefore concluded that the teratogenic activity of GF is unlikely to be associated with the release of formaldehyde in utero. However, GF bears a close structural similarity to the rodent teratogen, ethyleneglycol monomethylether (EGME), and this may provide a basis for understanding its teratogenic activity and for predicting similar activity for other cyclic ether alcohols.
Mutagenesis of L5178Y/TK+ / − −3.7.2C mouse lymphoma cells by the clastogen ellipticine
Authors: Moore Martha M. , Brock Karen H. , Doerr Carolyn L. , Demarini David M. 
Published: February 2007

AbstractEllipticine is a potent clastogen in CHO cells (Bhuyan et al: Cancer Res 32:2538–2544, 1972). The reported mutant frequencies produced by ellipticine at the hprt locus in CHO cells are ⩽50/106 survivors (background ∽ 2/106; survival = 10%) (DeMarini et al: Cancer Res 43:3544–3552, 1983; Singh and Gupta: Cancer Res 43:577–584, 1983; Environ Mutagen 5:871–880, 1983). In the present study, the mutagenic and clastogenic activities of ellipticine were evaluated in L5178Y/TK+/− −3.7.2C mouse lymphoma cells. Unlike the results at the hprt locus, ellipticine is a potent mutagen at the tk locus, with as little as 50 ng/ml producing an induced mutant frequency of 142/106 survivors (background = 56/106; survival = 61 %) and 198/106 survivors (background = 72/106; survival = 50%) in two separate experiments. This same dose of ellipticine induced 44 aberrations per 100 metaphases (background = 5/100 cells). At 400 ng/ml, ellipticine induced over 1,000 mutants /106 survivors at ∽ 10% survival and produced 242 aberrations/100 cells. Under the test conditions, most of the aberrations were chromosome rather than chromatid events. As expected for a compound acting primarily by a clastogenic mechanism, almost all of the TK‐deficient mutants were small colonies. Thus, ellipticine is a potent clastogen in both Chinese hamster cells and in mouse lymphoma cells; however, it is a potent mutagen at only the tk locus and not at the hprt locus. These results support.
Coffee is highly mutagenic in the L‐arabinose resistance test in Salmonella typhimurium
Authors: Dorado Gabriel , Barbancho Manuel , Pueyo Carmen 
Published: February 2007

AbstractThe present study shows that the L‐arabinose resistance test in Salmonella typhimurium detects coffee as a strong mutagen in the absence of mammalian microsomal activation. The response of the Ara forward mutation assay was 8.5 times higher than that of TA104, which is the most sensitive to coffee of the tester strains of the Ames test. Both the mutagenesis protocol (preincubation test) and the additional genetic characteristics of the bacterial tester strain (excision repair deficiency, normal lipopolysaccharide barrier, and the presence of plasmid pKM101) were critical factors in the optimal induction by coffee of forward mutations to L‐arabinose resistance. All ten samples of roasted coffee analyzed with the Ara assay were highly mutagenic: one cup of coffee (150 ml) was calculated to induce 3‐4 × 106 AraR mutants. In contrast, coffee prepared from unroasted beans (green coffee) had no mutagenic activity. Regular‐ and sugar‐roasted coffees showed similar mutagenicities, but the specific mutagenic activity of instant coffees (1559 AraR mutants/mg) was almost 2 times that of noninstant ones (834 AraR mutants/mg). The Ara assay allowed the direct testing of coffee, although it was demonstrated that lyophilization has no effect on the mutagenicity of this beverage. Like roasted coffee, roasted barley induced a large number of AraR mutants per mg (227), though its specific mutagenic activity was approximately 4 and 7 times lower than that of noninstant and instant coffees, respectively.
Lack of induction of nuclear aberrations by captan in mouse duodenum
Authors: Chidiac Peter , Goldberg Mark T. 
Published: February 2007

AbstractThe fungicide, captan, is known to induce point mutations in vitro. In extremely high doses, technical grade captan leads to duodenal tumors in mice. In short‐term in vivo assays for genotoxicity, equivocal results have been obtained with captan. In this study, the genotoxicity of captan was studied in vivo in the proximal small intestine of the mouse, the site of its oncogenicity. Orally administered captan up to 4,000 mg/kg body weight failed to induce a response in the small intestine nuclear aberration assay in a wide range of doses under a variety of experimental conditions, including pretreatment of animals with L‐buthionine‐S, R‐sulfoximine (an inhibitor of glutathione biosynthesis). 1,2,3,6‐Tetrahydrophthalimide and bis (trichloromethyl)disulfide, two compounds that have been identified as impurities in technical grade captan, also failed to produce positive results in this assay.
Acrylamide: Induction of heritable translocations in male mice
Authors: Shelby M. D. , Cain K. T. , Cornett C. V. , Generoso W. M. 
Published: February 2007

AbstractAcrylamide (AA), known to induce dominant lethals in male rodents, was studied in the mouse heritable translocation test by using intraperitoneal injections on 5 consecutive days. Matings on days 7‐10 following the last injection yielded a high frequency of translocation carriers in the F1 male population, which demonstrated that acrylamide is an effective inducer of translocations in postmeiotic germ cells. As an inducer of both dominant lethals and heritable translocations in late spermatids and early spermatozoa, AA is similar to alkylating agents such as ethylmethanesulfonate and ethylene oxide. However, AA′s chemical structure, the nature of adducts formed with DNA, and its lack of mutagenicity in bacteria suggest a different mechanism as the basis for AA′s germ cell mutagenicity.
Effects of radiofrequency radiation and simultaneous exposure with mitomycin C on the frequency of sister chromatid exchanges in chinese hamster ovary cells
Authors: Ciaravino Victor , Meitz Martin L. , Erwin David N. 
Published: February 2007

AbstractChinese hamster ovary (CHO) cells were exposed for 2 hr with and without mitomycin C (MMC) (1 × 10−8M) to pulsed wave radiofrequency radiation (RFR) at 2450 MHz. The repetition rate of 25,000 pulses per sec (pps), pulse width of 10 μs, and exposure geometry used, resulted in a specific absorption rate (SAR) of 33.8 W/kg. The following exposure regimens were used: 1) a 37°C water bath control; 2) a water bath temperature control (TC) in which the continuously monitored medium temperature closely followed the temperature rise in the RFR‐exposed flasks; and 3) the RFR‐exposed cells in a water bath set at 37°C prior to exposure. RFR exposure resulted in a maximum cell culture medium temperature of 39.2°C. In the absence of MMC, there was no significant increase in sister chromatid exchange (SCE) in the RFR‐exposed or TC groups over that of the 37°C control. When a simultaneous treatment of RFR and MMC occurred there was no statistical difference in SCE frequency from that caused by chemical treatment alone.
Vaporization technique to measure mutagenic activity of volatile organic chemicals in the ames/Salmonella assay
Authors: Hughes Thomas J. , Simmons Debra M. , Monteith Linda G. , Claxton Larry D. 
Published: February 2007

AbstractThe purpose of this research was to develop and characterize a sensitive test method to detect mutagenic activity of volatile liquid organic chemicals (i.e., volatiles) in the Ames/Salmonella assay. A Tedlar® bag vaporization technique was developed, which increased contact time between the volatiles and bacterial test system, circumvented volatilization limitations in the standard plate incorporation and preincubation methods, allowed chemical analysis during incubation, and was flexible in design.The vaporization technique was evaluated concurrently against the plate incorporation and preincubation techniques with eight liquid volatile mutagens in the Ames/Salmonella mutagenicity assay with Salmonella typhimurium strains TA100 and TA102. Results suggested that when volatile organic chemicals with boiling points below 63 °C were tested for mutagenic activity, the most sensitive test conditions were the vaporization technique with TA100. GC analysis of epichlorohydrin and butylene oxide concentrations within Tedlar® bags suggested that these two chemicals volatilized and were contained in the media after 1 hr of incubation at 37 °C. The mutagenic activity of six volatile liquid mutagens was similar in single and triple plate Tedlar® bags.Three general test groups of volatile organic chemicals were identified by test data: 1) chemicals which had boiling points below 63°C, for which the vaporization technique was the most sensitive test procedure (ethylene, propylene, and butylene oxides and methylene chloride); 2) chemicals which had boiling points from 1077 to 132°C, for which the vaporization technique was still useful, but where sensitivity was only slightly increased over the preincubation technique (1‐bromo‐2‐chloroethane, epichlorohydrin, and ethylene dibromide); and 3) a chem‐.