bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of unscheduled DNA synthesis in primary cultures of rat pancreatic cells following in vivo and in vitro treatment with genotoxic agents
Authors: Steinmetz Karen L. , Mirsalis Jon C. 
Published: February 2007

AbstractThe pancreas is a key target tissue in human and animal carcinogenesis, yet few short‐term test systems measure genotoxicity in pancreatic cells. A method has been developed for the measurement of DNA repair as unscheduled DNA synthesis (UDS) in primary cultures of rat pancreatic cells (PRP) following in vitro or in vivo exposures to chemicals. PRP were isolated from female Sprague‐Dawley (SD) or male Fischer‐344 rats by mincing the pancreas in a collagenase solution followed by digestion in dispase. For in vitro exposures, PRP were incubated with 3H‐thymidine (3H‐TdR) in the presence of genotoxic agents for 18–22 hr. For in vivo exposures, male Fischer‐344 rats were treated with genotoxic agents 2 hr prior to sacrifice of the animals, and cells were incubated with 3H‐TdR. UDS was measured by quantitative autoradiography as net grains/nucleus (NG). Solvent controls ranged from −1.0 to −2.8 NG. Cells isolated from female SD rats and treated in vitro with methylmethane sulfonate (MMS), ethylmethane sulfonate (EMS), N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), and the pancreatic carcinogen azaserine all yielded over 4.0 NG. Cells treated in vitro with the hepatocarcinogens 2‐acetylaminofluorene (2‐AAF) and dimethylnitrosamine (DMN) and with the multisite carcinogen benzo[a] pyrene (B[a]P) yielded between −1.0 and −3.3 NG. These results are consistent with the lack of carcinogenic activity of 2‐AAF, DMN, and B[a]P in the pancreas and indicate that pancreatic cells are incapable of metabolizing these compounds to genotoxic forms. In vivo treatment with MMS at 100 mg/kg yielded 1.9 NG and with azaserine at 100 mg/kg yielded 8.2 NG. This method should be useful in detecting agents that are genotoxic to the pancreas.
Mutagenicity screening of foods. II. Results with fruits and vegetables
Authors: Stoltz D. R. , Stavric B. , Stapley R. , Klassen R. , Bendall R. , Krewski D. 
Published: February 2007

AbstractA survey of the mutagenic potential of a wide variety of food products has been initiated with results for 28 different beverages reported previously [Stoltz et al, 1982b]. Here, results for samples of 46 widely consumed fruits and vegetables from six general categories are given. Each sample was concentrated and fractionated by polarity and solubility to give five fractions, each of which was assayed for mutagenic potential withSalmonella typhimuriumTA98 and TA100. Although statistical analysis of the data resulted in positive findings for 22 fruit and vegetable samples, only six products (grapes, onions, peaches, raisins, raspberries, strawberries) demonstrated potent mutagenic activity.
The relationship between lethal mutation yield and intake of ethylnitrosourea (ENU) in Drosophila melanogaster
Authors: Ayaki Toshikazu , Ohshima Kayoko , Okumura Yutaka , Yoshikawa Isao , Shiomi Toshio 
Published: February 2007

AbstractTo estimate the absorbed dose of N‐ethyl‐N‐nitrosourea (ENU) ingested in Drosophila melanogaster, males were fed with sucrose solutions containing various concentrations of ENU plus 3H‐labeled sucrose for 24 hr. Flies showed decreasing intakes with increase in ENU concentration when monitored by intake 3H radioactivity. Absorbed dose, D, per male can be estimated by the following formula: D = vμ C, where v is intake volume per male of sucrose solution at concentration C. Estimating the v value for each ENU solution from 3H radioactivities in male flies, and using the above formula, we reached the conclusion that average absorbed doses of ENU were 0.064, 0.221, and 0.302 nmol, respectively, for the ENU concentrations of 0.03, 0.3, and 1.0 mM. Sex‐linked recessive lethals were measured for males exposed to these sucrose solutions at three different ENU concentrations. Their frequencies increased nonlinearly with increasing exposure doses—ie, ENU concentration C—but linearly with increasing absorbed doses estimated in the above‐mentioned way.
Microbial mutagenicity of isomeric two‐, three‐, and four‐ring amino polycyclic aromatic hydrocarbons
Authors: Later Douglas W. , Pelroy Richard A. , Stewart Dorothy L. , McFall Ten , Booth Gary M. , Lee Milton L. , Tedjamulia Marvin , Castle Raymond N. 
Published: February 2007

AbstractThe isomers of various two‐, three‐, and four‐ring amino polycyclic aromatic hydrocarbons were tested for mutagenic activity using a microbial plate incorporation test with four Salmonella typhimurium strains (TA98, TA 100, TA1535, and TA 1537). All compounds were assayed with an S9 metabolic activating enzyme system. The two‐ring compounds were tested only with TA98. All were weakly mutagenic (1–10 rev/μg) except 2‐aminobiphenyl, which was not mutagenic under these test conditions. All except two of the 13 fused three‐ring compounds (aminofluorenes, aminoanthracenes, and aminophenanthrenes) were active frame shift mutagens; only the aminophenanthrenes were active base‐pair mutagens. The potency of this group of isomeric compounds ranged from moderately (˜ 20 rev/μg) to strongly (> 5,000 rev/μg) mutagenic. As a group, the pericondensed fourring amino compounds were the most mutagenic of the three groups tested. All of the aminofluoranthene and aminopyrene isomers showed significant mutagenic activity with TA98, TA100, and TA1537. In general, the mutagenic potency of the amino polycyclic aromatic compounds tested was highly dependent on the structural position of the amino group.
In vivo persistence of sister chromatid exchanges (SCE) induced by gamma rays in mouse bone marrow cells
Authors: Morales‐Ramírez Pedro , Vallarino‐Kelly Teresita , Rodriguez‐Reyes Regina 
Published: February 2007

AbstractThe sister chromatid exchange (SCE) frequencies induced in bone marrow cells by in vivo irradiation with gamma rays before or after bromodeoxyuridine (Brdurd) incorporation were compared. The frequency of SCE at different postir‐radiation times was also measured in bone marrow cells in vivo, irradiated before Brdurd incorporation. Increased sensitivity to SCE induction by radiation was found in cells after Brdurd incorporation for one cycle when compared with cells irradiated before Brdurd incorporation. The increased SCE frequency persisted for at least 72 hr after the initial irradiation, implying that the gamma ray‐induced lesion(s) capable of eliciting an SCE are persistent and cannot be easily repaired.
Reduced mutant yield at high doses in the Salmonella/activation assay: The cause is not always toxicity
Authors: McGregor Douglas , Prentice Robert D. , McConville Malcolm , Lee Young Jack , Caspary William J. 
Published: February 2007

AbstractIn the Salmonella/activation assay developed by Ames et al [1973, 1975] toxicity is not measured, though it is recognized by the loss of a cloudy appearance on the plate. One approach to the measurement of toxicity is described here and uses a microscope‐linked automated colony counter to estimate the number of micro‐colonies formed by histidine auxotrophs that stop growing after the depletion of histidine. This technique was used to evaluate the effect of toxicity on the revertant count for 16 mutagens, most of which were chosen because, from previous experience, their dose‐response curves manifested a maximum at an intermediate dose tested.One of the sixteen, 2‐nitrofluorene, was not toxic up to the maximum dose tested. The relationship between mutation and toxicity for the remaining fifteen allowed them to be grouped into two categories: (1) compounds that induced decreases in survival at the same dose at which the number of mutants decreased, and (2) compounds that induced toxicity, but survival was reduced at dose levels higher than those required to reduce the number of mutants. Possible explanations for this reduction of mutant counts occurring with little apparent concomitant increase in toxicity are examined. These results may be significant for attempts to estimate mutagenic potency and, to a lesser extent, construct mathematical models of the Ames test.
Enhancing activity of rat tissue extracts for induction of lambda prophage by L‐azaserine
Authors: Suit J. L. , Cruz B. Miranda‐Da , Sito L. , Rogers A. E. 
Published: February 2007

AbstractWe studied the effect of rat tissue extracts on induction of lambda prophage in Escherichia coli (λ) by L‐azaserine. Hepatic and pancreatic extracts, primarily the cytosolic fraction, markedly increased the rate of induction. Hepatic extracts from lipotrope‐deficient rats were somewhat more active than extracts from normal rats. The enhancing activity in normal rat hepatic cytosol was partially characterized. It reduced by about one‐half the dose of azaserine required for a given purpose. The enhancement was increased by preincubating the bacterial cells with cytosol; cells retained the effect after cytosol was removed. Enhancing activity was inhibited strongly by the amino acids phenylalanine, tryptophan, and tyrosine; to lesser extents by leucine, methionine, and serine; and not at all by proline or glutamine. It was eliminated by dialysis of the cytosol and reduced by omission of nicotinamide adenine dinucleotide phosphate (NADP) from the reaction mixture. Heating the cytosol to 60°C or 80°C or varying the pH of the reaction mixture from 6 to 8 had no significant effect. Treating the cytosol with trypsin appeared to release an inhibitor of the activity. Glutathione, cysteine, and β‐mercaptoethanol also enhanced X induction by azaserine, but the cytosolic activity was not affected by the thiol‐inactivating compound diethylmaleate (DEM). The results suggest that factors in cytosol interact with bacterial cells to facilitate transport of azaserine into the cells, primarily through the aromatic amino acid transport system. A small molecule, not a free thiol compound, appears to be involved. It may serve to establish reducing conditions protective for azaserine, the probable mechanism of action of sulthydryl compounds.
Lack of effect of dibromochloropropane on the mouse testis
Authors: Oakberg E. F. , Cummings C. C. 
Published: February 2007

AbstractA single intraperitoneal injection of (101 x C3Hf)F male mice with 110 mg/kg of 1,2‐dibromo‐3‐chloropropane (DBCP) showed no effect on spermatogonial stem cells or on differentiating spermatogonia as measured by cell counts made 3, 5, and 8 days after injection.
A comparison of genotoxicity of automotive exhaust particles from laboratory and environmental sources
Authors: Brooks A. L. , Li A. P. , Dutcher J. S. , Clark C. R. , Rothenberg S. J. , Kiyoura R. , Bechtold W. E. , McClellan R. O. 
Published: February 2007

AbstractThis research (1) ranked the genotoxicity of methylene chloride extracts of laboratory and environmentally collected particles and (2) evaluated the role of collection location and sample composition on genotoxic potency. Samples of exhaust from a spark‐ignition automobile, light‐duty diesel automobile, and a heavy‐duty diesel engine operated in a laboratory on a dynamometer were studied, as well as samples taken in a highway tunnel and outside the same tunnel. The tunnel samples were collected 30 m inside or 56 m outside the exit portal at times when between 70%‐95% of the traffic consisted of diesel trucks. In the Ames Salmonella mutagenicity assay, each extract produced a dose‐dependent increase in mutagenicity in strain TA‐98 without addition of liver S‐9 fraction. Extracts from two tunnel samples collected 1 yr apart, and extracts of particles collected outside the tunnel had similar mutagenic activity. The order of mutagenic activity per μg of extract in TA‐98 without S‐9 from the lowest to the highest was environmental sample ⩽ tunnel < heavy‐duty diesel < light‐duty diesel < spark ignition. Addition of S‐9 or testing in Salmonella strains resistant to the mutagenicity of nitroaromatic compounds (TA‐98 NR and TA‐98 1,8‐DNP6) decreased the mutagenic response. With cell killing, sister chromatid exchanges, and mutations as endpoints in Chinese hamster ovary cells (CHO), the order of potency was tunnel < light‐duty < spark‐ignition samples. All three extracts induced a similar amount of mitotic delay per μg with or without S‐9. Enhanced chromosome aberration frequency was detected only in cells exposed to extracts from sparkignition exhaust. The data indicated that genotoxic activity was detected in each particle extract, that the potency ranking was similar using different genetic endpoints, and that the magnitude of the genotoxic potency was similar.
Mutagenicity of azo dyes following metabolism by different reductive/oxidative systems
Authors: Reid Thomas M. , Morton Kenneth C. , Wang Ching Y. , King Charles M. 
Published: February 2007

AbstractThe mutagenic activity of a group of diazo dyes based on benzidine and its congeners was compared following metabolic activation of the dyes through sequential reduction and oxidation. The dyes were reduced by incubating them with either a suspension of rat cecal flora or a hamster S9 mix supplemented with flavin mononucleotide. The products of dye reduction were then subjected to oxidative metabolism by either Aroclor‐induced rat liver S9 or by hamster liver S9; the resultant mutagenic activity was assayed with Salmonella typhimurium TA1538. Fifteen of the 17 compounds tested were mutagenic, and the degree of mutagenicity was affected by the activity of both the reduction and oxidation systems used. Purified dyes required a reductive step to become mutagenic, but several of the crude dyes did not. All the positive compounds, however, were more mutagenic when the reduction step was included. The mutagenicity of the purified dyes was equal to or greater than that of an equimolar amount of benzidine or appropriate benzidine congener. For the crude dyes, there were no consistent quantitative relationships between the mutagenicity of the dye and that expected from the benzidine moiety.
Calibration of the maize yg2 assay using gamma radiation and ethylmethanesulfonate
Authors: Plewa Michael J. , Dowd Patrick A. , Wagner Elizabeth D. 
Published: February 2007

AbstractA standard protocol for the yellow‐green‐2 (yg2) forward mutation assay in Zea mays is proposed. A detailed calibration of the assay using 137Cs gamma rays and ethylmethanesulfonate (EMS) was conducted. Gamma ray‐induced mutant sectors in leaves 4 and 5 exhibited one‐hit kinetics. The radiation doses ranged from 25 to 500 rads. The mean induced mutation rate per rad of gamma radiation was 4.54 × 10−6. This value was constant for the primordial cells of leaves 4 or 5. The induction of forward mutation by EMS also exhibited one‐hit kinetics in the concentration range 0.25–20 mM (0.33–23.54 μmol EMS/kernel). The mean induced mutation rate per mM EMS was 1.79 × 10−4, and the mean induced mutation rate per μmol of EMS per kernel was 1.52 × 10−4. Using the induced mutation rates for gamma radiation and EMS, the rad equivalent was calculated. One rad of gamma radiation is equivalent to the exposure of a 2.53 × 10−5 M EMS solution or to 2.99 × 10−8 mol of EMS per kernel.
Evaluation of the genotoxicity of process stream extracts from a coal gasification system
Authors: Shimizu R. W. , Benson J. M. , Li A. P. , Henderson R. F. , Brooks A. L. 
Published: February 2007

AbstractExtracts of three complex organic environmental mixtures, two from an experimental coal gasifier (a raw gas and a clean gas sample) and one from a coke oven main, were examined for genotoxicity. Three short‐term genotoxicity assay systems were used: Ames Salmonella typhimurium reverse mutation assay, Chinese hamster ovary cell/hypoxanthine‐guanine phosphoribosyl transferase (CHO/ HGPRT) gene locus mutation assay, and the Chinese hamster lung primary culture/sister chromatid exchange (CHL/SCE) assay. Aroclor‐1254‐induced rat liver homogenate fraction (S‐9) was required to observe genotoxicity in both gene locus mutation assays (CHO/HGPRT and Ames). The relative survival of CHO cells exposed to extracts was highest in cells exposed to clean gas samples, with the raw gas sample being the most cytotoxic either with or without the addition of S‐9. All three complex mixtures induced sister chromatid exchanges in primary lung cell cultures without the addition of S‐9. The relative genotoxicity ranking of the samples varied between the mammalian and prokaryotic assay systems. Coke oven main extract produced fewer revertants in bacteria than the raw gas sample. However, the coke oven main extract was more genotoxic in the two eukaryotic systems (CHL/SCE and CHO/HGPRT) than was the raw gas sample. The results of all three assays indicate that the cleanup process used in the experimental gasifier was effective in decreasing the genotoxic materials in the process stream. These data also reemphasize the necessity of evaluating genotoxicity of complex mixtures in a variety of short‐term systems.
Detoxification of nitrosamides and nitrosocarbamates in blood plasma and tissue homogenates
Authors: Aukerman Sharon Lea , Brundrett Robert B. , Hartman Philip E. 
Published: February 2007

AbstractNitrosamides and nitrosocarbamates exhibit relatively high mutagenic activity in Salmonella when compared with nitrosoureas. This high activity can be accounted for by activation of nitrosamides and nitrosocarbamates by cellular thiols, predominantly reduced glutathione, that are present intracellularly at concentrations in the millimolar range. In striking contrast to the in vitro mutagenicity tests, a number of studies have indicated that nitrosamides and nitrosocarbamates are less potent than nitrosoureas when tested in vivo in model systems such as the mouse. We extend here previous studies [Aukerman et al, 1983] that demonstrate striking chemical decomposition and inactivation of mutagenic activity of nitrosamides and nitrosocarbamates during exposure to murine blood plasma. Plasma glutathione concentrations are inadequate to account for the rapid inactivations noted. Furthermore, the predominant inactivating species is heat‐sensitive, nondialyzable, and is greater than 25,000 daltons in size as judged by ultrafiltration experiments. Serum albumin has some inactivating capacity at the concentration found in undiluted plasma and could account for the very low but significant inactivating capacity of human plasma. On the other hand, serum albumin lacks the potency necessary to account for the extremely high levels of inactivating activity observed in rodent and rabbit plasma. Elsewhere we present evidence that carboxylesterase activity is the predominant inactivating species in mouse plasma [Aukerman et al, 1983; Aukerman, 1983; Brundrett and Aukerman, 1984]. Mouse liver, large intestine, kidney, and stomach have more activity per milligram protein under the assay conditions used than plasma itself. Rat liver S9 is also active at enhancing the decomposition of nitrosamides and nitrosocarbamates; most of this inactivating capacity resides in the microsomal fraction. The relatively rapid detoxification of these N‐nitroso compounds by plasma and other tissues of rodents has important implications regarding the utility of rodents in assessment of tumorigenicity and/ or antitumor activity of these classes of drugs in other animal species. Tests with Salmonella may be of use in estimating relative levels of protection that vary widely among mammalian species.
Chemicals showing no evidence of carcinogenicity in long‐term, two‐species rodent studies: The need for short‐term test data
Authors: Shelby Michael D. , Stasiewicz Stanley 
Published: February 2007

AbstractStudies to determine the performance of short‐term tests (STT) in predicting chemical carcinogenicity are frequently characterized by a poor representation of noncarcinogens among the test chemicals. As a result, the performance of several STT is well characterized with carcinogenic chemicals, but the ability of the tests to discriminate between carcinogens and noncarcinogens is largely unknown because of the shortage of test results for noncarcinogens.A list of 70 chemicals that have been tested by the National Cancer Institute or the National Toxicology Program in long‐term rodent carcinogenicity studies and that have yielded no evidence of cancer induction in male and female rats and mice is presented. The list helps document the shortage of STT results of noncarcinogens and provides a potential source of chemicals for consideration in future studies designed to assess the ability of STT to predict chemical carcinogenicity.
Chemical mutagenesis testing in Drosophila. II. Results of 20 coded compounds tested for the national toxicology program
Authors: Zimmering S. , Mason J. M. , Valencia R. , Woodruff R. C. 
Published: February 2007

AbstractResults are presented from mutagenesis testing in Drosophila of 20 coded compounds. Two compounds were positive in the sex‐linked recessive lethal test, and two were inconclusive. The positive compounds were calcium chromate in adult feeding experiments and ferrocene after adult injection. The two inconclusive compounds were 2,4‐diaminophenol dihydrochloride and hexachiorocyclopentadiene. Compounds that produced a positive response were assayed for chromosome breakage using the conventional translocation test. Calcium chromate was negative in the translocation test, and ferrocene was positive. Many of the test compounds were poorly soluble in water, raising questions regarding the effective concentration to which the flies were exposed.
Effects of some DNA‐ligands and of some mutagenic compounds on the induction of meiotic disomic or diploid yeast products
Authors: Sora Silvio 
Published: February 2007

AbstractData were collected following the administration of various compounds to meiotic yeast cultures to investigate their effects on disomic or diploid induction. Epi chlorohydrin, actinomycin D, and 9‐aminoacridine were unable to induce either diploidy or disomy. Ethyl methanesulphonate was active in inducing diploids, while hycanthone induced disomics. β‐Propiolactone, N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, and β‐naphtylamine were able to increase both disomy and diploidy.
Evaluation of chemicals used for drinking water disinfection for production of chromosomal damage and sperm‐head abnormalities in mice
Authors: Meier John R. , Bull Richard J. , Stober Judy A. , Cimino Michael C. 
Published: February 2007

AbstractChemical oxidants are commonly added during water treatment for disinfection purposes. These chemicals have not been tested previously for their ability to induce genetic damage in vivo. Chlorine (hypochlorite and hypochlorous acid), monochloramine, chlorine dioxide, sodium chlorite, and sodium chlorate were evaluated for induction of chromosomal aberrations and micronuclei in bone marrow of CD‐I mice, and for induction of sperm‐head abnormalities in B6C3F1 mice. Oral administration of chlorine at pH 8.5 (where hypochlorite predominates) at dose levels equivalent to approximately 4 and 8 mg/kg/day induced significant increases in the level of sperm‐head abnormalities. There was no evidence of other effects with any of the disinfectants. Halogenated acetonitriles, which have previously been shown to form in the stomach following oral dosing of sodium hypochlorite to rats, were also tested in the sperm‐head abnormality assay but gave no indication of an effect.
Mutagenicity testing of Di(2‐ethylhexyl)phthalate and related chemicals in Salmonella
Authors: Zeiger Errol , Haworth Steve , Mortelmans Kristien , Speck William 
Published: February 2007

AbstractDi(2‐ethylhexyl)phthalate and 33 other phthalates, ethylhexanol derivatives, and related chemicals were tested for mutagenicity in Salmonella typhimurium strains TA98, TA 100, TA 1535, and TA 1537 without metabolic activation and in the presence of rat and hamster liver S‐9 metabolic activation systems. No mutagenic activity was seen with any of the chemicals tested.