bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear relationship between lethal mutation yield and intake of ethyl methanesulfonate in Drosophila melanogaster
Authors: Ayaki Toshikazu , Oshima Kayoko , Yoshikawa Isao 
Published: February 2007

AbstractMales of Drosophila melanogaster were fed sucrose solutions containing various concentrations of EMS (from 0.25 to 10 mM) for 24 hr. To measure the intake of an EMS solution, 3H‐labeled sucrose was added to the feeding solution, and the 3H activity inside the flies was used as a measure for the intake volume of EMS solution. Each absorbed dose of EMS was estimated from the intake volume of an EMS solution multiplied by its EMS concentration in the feeding solution in a way similar to that described in a previous report [Ayaki et al, 1984]. The relationship between the estimated absorbed dose and the exposure concentration was almost linear in a low concentration range but became concave with a downward curvature in a high concentration range. The dose‐response relationship between the frequency of sex‐linked recessive lethals and the estimated absorbed dose showed no deviation from linearity at all the five absorbed doses tested. It may be concluded that the absorbed doses thus estimated were very close to true absorbed doses, indicating the usefulness of the present method for dosimetry of chemicals to be given to flies.
SCE induction is uncoupled from mutation induction in mammalian cells following exposure to ethylnitrosourea (ENU)
Authors: Stetka Daniel G. , Bleicher William T. , Brewen J. Grant 
Published: February 2007

AbstractIt has been suggested not only that sister chromatid exchange (SCE) induction might serve as a qualitative indicator of mutagenesis, but also that induced SCE frequencies are linearly related to induced mutation frequencies. The consistency of the relationship between SCEs and mutations was tested in the present work. Confluent Chinese hamster ovary (CHO) cells were exposed to ethylnitrosourea (ENU) and then held at confluency for various times prior to initiation of SCE and mutation assays. Cells held at confluency are typically thought to be arrested in their progression through the cell cycle, so that “S‐dependent” processes such as fixation of mutations and formation of SCEs will not occur, while DNA repair processes might continue to operate. If repair processes reduce the number of SCE‐inducing lesions during the holding period and, hence, reduce the subsequently determined SCE frequencies, then mutation frequencies should similarly be reduced if SCEs and mutations are related. It was observed, however, that induced SCE frequencies decreased exponentially with holding time, while mutation frequencies remained constant. Qualitatively similar results were obtained in log‐phase cells. Cell cycle analysis demonstrates that confluent CHO cells can cycle, and ways are considered in which this might affect SCE and mutation frequencies. It is concluded that the decline in SCE frequency (with time) cannot be attributed solely to the presence of cycling cells in confluent cultures. It appears, therefore, that at least some forms of ENU‐induced DNA damage that can lead to SCE were repaired and as such are distinct from those forms that are mutagenic. Thus SCEs are not necessarily related to mutations, because the two events may represent manifestations of different forms of DNA damage. Whether or not this represents a universal phenomenon that would hold true for agents other than ENU remains to be determined.
Genotoxicity of the cooked‐food mutagens IQ and MeIQ in primary cultures of rat, hamster, and guinea pig hepatocytes
Authors: Loury David J. , Byard James L. 
Published: February 2007

AbstractTo investigate possible interspecies differences in the hepatocellular genotoxicity of the food‐borne mutagens 2‐amino‐3‐methyl‐imidazo[4,5‐f]quinoline (IQ) and 2‐amino‐3,4‐dimethyl‐imidazo[4,5‐f]quinoline (MeIQ), primary cultures of rat, hamster, and guinea pig hepatocytes were established. The induction of DNA repair activity in cultures exposed to various concentrations of IQ and MeIQ was determined by liquid scintillation spectrometry. DNA repair responses to MeIQ were, in general, greater than those elicited by IQ. In all three preparations of rat and hamster hepatocytes and in two of three preparations of guinea pig cells, MeIQ produced statistically significant (p <0.05) repair responses. IQ stimulated significant levels of repair in all three rat hepatocyte preparations and in two of three hamster cell preparations. In guinea pig cells exposed to IQ, no significant repair activity was observed. These results indicate that the genotoxicity of IQ and MeIQ in hepatic cells in species‐dependent.
The stability of mutagenic chemicals stored in solution
Authors: Pagano Dennis A. , Zeiger Errol 
Published: February 2007

AbstractUsing the Salmonella/microsome assay, we have evaluated the stability of mutagenic responses of chemicals stored frozen over a period of 18 months. Each of the standard mutagens was prepared in January 1982, and aliquots were stored at −20°C and at −80°C. Sodium azide (NaN3) was dissolved in water; 4‐nitro‐o‐phenylenediamine (4NOP), 4‐nitroquinoline‐N‐oxide (4NQO), benzo(a)pyrene (B[a]P), and 2‐aminoanthracene (2AA) were dissolved in DMSO, all at 100 μg/ml. At various times, aliquots were removed, thawed, and tested in parallel with freshly prepared mutagen samples using strain TA100 in a standard plate test and freshly prepared Aroclor 1254‐induced rat liver S‐9 mix where needed. 4NOP (2–10 μg/plate), 4NQO (0.01–0.10 μg/plate), B(a)P (0.5–2.5 μg/plate), and 2AA (0.25–2.0 μg/plate) showed no significant differences between the freshly prepared solutions and the solutions stored at −20°C and −80°C. NaN3 (0.1–0.8 μg/plate) did show a statistically significant difference, with the fresh samples giving the lowest mean responses (over all doses) and the −80°C treatment giving the highest.The freezing of mutagen solutions is adaptable to routine use and provides the advantage of reducing the time required to prepare positive control chemicals and reducing the exposure of laboratory personnel to known mutagens.
Metabolic activation of 3‐(2‐chloroethoxy)‐1,2‐dichloropropene: A mutagen structurally related to diallate, triallate, and sulfallate
Authors: Distlerath Linda M. , Loper John C. , Wilson Tabor M. 
Published: February 2007

Abstract3‐(2‐Chloroethoxy)‐1,2‐dichloropropene (CP), a Salmonella promutagen that was recently isolated from a sample of residue organics previously concentrated from drinking water, is structurally related to three other chlorinated promutagens, the S‐chloroallyl thiocarbamate herbicides diallate, triallate, and sulfallate. These four chloroallyl ether compounds were found to be similar with respect to strain specificity, potency, and requirement for specific metabolic activation. The 9,000g supernatant (S9) fractions from polychlorinated biphenyl Aroclor 1254‐ or phen‐obarbital‐induced rats metabolized the four chloroallyl ethers to mutagenic products, whereas S9 from 3‐methylcholanthrene‐induced or uninduced rats did not. The metabolic activation of CP, diallate, and triallate to mutagens was catalyzed by the 100,000g microsomal pellet of S9 alone, but the activation of sulfallate to mutagenic metabolites required both microsomal and cytosolic fractions of S9. Direct‐acting (minus S9) mutagenic metabolites of diallate and triallate could be extracted into methylene chloride from S9 incubation mixtures. Incubations containing S9 and either sulfallate or CP did not yield methylene chloride‐extractable metabolites with direct‐acting mutagenic activity. On the basis of these results and those from previous studies on the metabolism of diallate, triallate, and sulfallate, a tentative model for the metabolic activation of CP is proposed in which this chloroallyl ether undergoes α‐carbon hydroxylation to form multiple mutagenic products.
Chemical mutagenesis testing in drosophila. IV. Results of 45 coded compounds tested for the national toxicology program
Authors: Yoon J. S. , Mason J. M. , Valencia R. , Woodruff R. C. , Zimmering S. 
Published: February 2007

AbstractResults from Drosophila mutagenicity tests of 45 chemcial compounds assayed for the National Toxicology Program are presented. Nine compounds were judged positive and four equivocal in the sex‐linked recessive lethal test. The nine positive compounds were acetin, allyl glycidyl ether, cyclophosphamide, 1,2‐dibromo‐3‐chloropropane, 2,3‐dibromo‐1‐propanol, dimethylcarbamyl chloride, 1,2‐epoxybutane, lasiocarpine, and N‐nitrosopiperidine. The results for chloral hydrate, maleic hydrazide, propantheline bromide, and trifluralin were equivocal. Of the nine compounds positive in recessive lethal induction, only two—allyl glycidyl ether and dimethylcarbamyl chloride—failed to induce translocations. The remaining 32 were judged to be nonmutagenic under the conditions used.
Petroleum distillates suppress in vitro metabolic activation: Higher [S‐9] required in the salmonella/microsome mutagenicity assay
Authors: Carver J. H. , Machado M. L. , Macgregor J. A. 
Published: February 2007

AbstractTo determine if standard conditions used in the Salmonella/mammalian microsome mutagenicity assay could reliably screen complex petroleum samples, two high‐boiling (700–1,070°F) distillates and their separated aromatic fractions were tested. The initial mutagenic activities were inconsistent with the samples' known polyaromatic hydrocarbon (PAH) contents and observed potencies in a dermal carcinogenesis bioassay. A significant mutagenic response was observed only at S‐9 concentrations 5 to 10 times higher than those used in the standard assay, supporting the use of elevated levels of S‐9 in the Salmonella/microsome assay to assess the carcinogenic potential of petroleum‐derived materials. All four samples masked the expected mutagenic activity of added PAHs (benzo[a]pyrene and perylene). Data suggested that petroleum distillates suppress the functional efficacy of the S‐9; possible mechanisms are discussed.
Aneuploidy and health risk assessment: Current status and future directions
Authors: Dellarco Vicki L. , Mavournin Kathleen H. , Tice Raymond R. 
Published: February 2007

AbstractThe U.S. Environmental Protection Agency (EPA) recently sponsored a workshop† to discuss (1) the contribution of aneuploidy to human disease and disability, (2) the development of tests for detecting chemicals that induce aneuploidy and the relevance of these tests to human risk, and (3) the current understanding of mechanisms by which aneuploidy arises. This summary is based on the presentations given at the workshop. It is hoped that this summary will stimulate thinking in this vitally important area of risk assessment and contribute to the establishment of priorities for basic research, development of new test methods, and validation of existing test approaches. Such research is needed to enhance the scientific basis of risk assessment for aneuploidy‐producing chemicals.
First‐generation litter‐size reduction following irradiation of spermatogonial stem cells in mice and its use in risk estimation
Authors: Selby P. B. , Russell W. L. 
Published: February 2007

AbstractLitter‐size reduction (LSR) is a useful measure of part of the overall F1 radiation‐induced damage. Extensive LSR data were obtained as a by‐product of specific‐locus experiments. Fourteen such experiments involving 158,490 F1 litters have been analyzed for the extent of LSR induced by x‐ or gamma‐irradiation of spermatogonia. Litter sizes were compared between experimental and control groups at about 3 weeks after birth. In order to reduce variability, comparisons were made only with concurrent controls and between groups of litters having mothers of approximately the same age. At the high dose rate of 90 R/min, the LSRs showed a humped dose‐response curve. There was a pronounced dose‐rate effect, the mutational responses being much less at dose rates of 0.009 R/min and 0.001 R/min. It is estimated that if men were exposed to 1 R of radiation delivered at low linear energy transfer (low LET) and low dose rate, the number of deaths caused by induced dominant mutations among their children before late childhood would be about 19 per million live‐born. This can be added to the earlier estimate of an approximately equal number of viable disorders in all body systems as based on dominant skeletal mutations. This gives a total estimate of induced dominant damage, but much of this addition represents death in very early embryonic life that would not be recognized in humans. The LSR data also permit the conclusion that only an extremely small proportion of serious radiation‐induced genetic disorders among live‐born humans would be expected to result from segmental aneuploidy.
Mutagenicity of the fractionated organic emissions from diesel, cigarette smoke condensate, coke oven, and roofing tar in the ames assay
Authors: Austin Ann C. , Claxton Larry D. , Lewtas Joellen 
Published: February 2007

AbstractMobile and stationary combustion sources emit particle‐bound organics that, after extraction, are mutagenic to Salmonella typhimurium. In this study, the organic emissions from diesel, cigarette smoke condensate (CSC), coke oven, and roofing tar were fractionated and compared for mutagenicity in the Ames assay. This study demonstrated major differences in the distribution of mutagenicity among the four emission sources. Within each source, the relative mutagenicity of each fraction was significantly different in the presence and absence of an exogenous metabolic activation. In the diesel sample, over 90% of the mutagenic activity is located in the aromatic and polar neutral (PN) fractions; nitrated polynuclear aromatic hydrocarbons (NO2‐PNAs) can account for a significant portion of this activity. Most of the mutagenicity of the coke oven main sample was found in the organic base (BASE) and PN fractions, which contained aromatic amines and nitrogen heterocycles. The CSC sample also had a high percentage of the mutagenic activity in the BASE fraction. Chemical analysis, however, indicates that the components in the CSC differed from those of the coke oven main sample. The roofing tar sample, which was not mutagenic in the absence of metabolic activation, contained several components that were very mutagenic after fractionation. This may be due to the separation of toxic components from the mutagenic components. The roofing tar emissions contained aromatic and polar mutagenic constituents. Although the specific mutagens in these different sources are not identical, they all cause frameshift mutations and appear to be compounds that could be classified as polycyclic organic matter.
The metabolic activation of 4,4′‐methylene‐bis‐(2‐chlorobenzeneamine) to a bacterial mutagen by hepatic postmitochondrial supernatant from human and other species
Authors: Cocker John , Boobis Alan R. , Gibson Jane F. , Davies Donald S. 
Published: February 2007

Abstract4,4′‐Methylene‐bis‐(2‐chlorobenzeneamine) (MbOCA) is a commercially important industrial chemical that is carcinogenic in three animal species and mutagenic in the Ames test. The ability of hepatic postmitochondrial supernatant from humans, dogs, mice, and rats to activate MbOCA to a bacterial mutagen has been investigated using the Ames plate incorporation test and a bacterial fluctuation test. In the Ames plate test, hepatic S9 preparations from mice and Aroclor 1254‐induced rats only were sufficiently active to produce a significant mutagenic response. Preincubation of MbOCA with S9 from human liver produced a slight increase in the number of revertants but not a doubling as compared to controls. However, using the more sensitive bacterial fluctuation test, liver S9 from all species activated MbOCA to a bacterial mutagen. The responses produced were dose‐related and, for at least part of the dose range, were double the background levels observed in controls. The increases in the mutagenicity of MbOCA produced by liver S9 from humans, dogs, and rats were significant at the 0.1% level of probability. Liver S9 preparations from all species in which MbOCA is carcinogenic have now been demonstrated to be capable of activating this compound to a bacterial mutagen. The finding that S9 from human liver can also activate MbOCA to a mutagen increases the concern that it may be a human carcinogen.
Chromosome fragments and other abnormalities induced by mitomycin C in the neuroblast of chortophaga viridifasciata
Authors: Ferguson Martha J. , Gaulden Mary Esther , Seibert G. Burton 
Published: February 2007

AbstractMitomycin C (MMC) induces acentric chromosome fragments in the neuroblast (Nb) of the grasshopper embryo (Chortophaga viridifasciata) after acute and chronic exposure to concentrations ranging from 10−8 to 10−4 M, the dose response being essentially linear up to 10−5 M. Because Colcemid is not used in the Nb assay, it was possible to detect two additional effects of MMC: (1) Prolonged retardation of many cells occurs when they reach very late prophase; the chromosomes continue condensing and lose their orderly prophase orientation, and the nuclear envelope becomes increasingly fragile. Such cells, which were observed after both acute and chronic exposure, give the false impression of being c‐metaphases when they are fixed and squashed. The frequency of retarded very late prophases and the duration of retardation are related to MMC concentration and time of exposure. A rationale is presented supporting the idea that the events associated with retarded very late prophase result from MMC effects on the nuclear envelope. (2) MMC significantly increases the frequency of Nb's with attenuated centromeres at the beginning of early anaphase, an effect that appears to be caused by a delay in the repulsion of sister chromatids that usually occurs immediately after centromere separation begins.
Validation of an in vivo alkaline elution assay to detect dna damage in rat testicular cells
Authors: Skare Julie A. , Schrotel Karen R. 
Published: February 2007

AbstractAn alkaline elution assay was used to measure DNA damage in the rat testis after in vivo treatment with chemicals. All of the chemicals reported to induce heritable mutations in a mammalian assay (mouse specific locus test) were positive in the rat alkaline elution assay. Chemicals that are negative or inconclusive in the specific locus test did not cause detectable DNA damage in rat testes. DNA damage was detected by alkaline elution after either intraperitoneal or oral administration of chemical mutagens. Data from these validation studies were used to establish criteria to be used for evaluation of alkaline elution results with materials of unknown potential for genotoxic effects in germinal tissue.
Computer analysis of toxicological data bases: Mutagenicity of aromatic amines in Salmonella tester strains
Authors: Klopman G. , Frierson M. R. , Rosenkranz H. S. 
Published: February 2007

AbstractThere is an increasing problem in the world of toxicological evaluation in that, while test results of new compounds are appearing regularly, traditional methods of analysis of such data are cumbersome and slow. The new computer program CASE (computer automated structure evaluator) was designed to handle just such problems. It analyzes molecules and their associated biological activity on the basis of structural fragments found and identified by the program as being important for the activity based on statistical tests of significance. The program was used to examine mutagenicity in Salmonella typhimuriwn strains TA98 and TA 100 (with S9 activation) of approximately 80–100 aromatic amines. The resulting structural features were then used in a predictive fashion to test the expected mutagenic properties of a smaller set of about 20 compounds.
Chemical mutagenesis testing in Drosophila. V. Results of 53 coded compounds tested for the national toxicology program
Authors: Woodruff R. C. , Mason J. M. , Valencia R. , Zimmering S. 
Published: February 2007

AbstractFifty‐three chemicals were tested for mutagenicity in Drosophila melanogaster by adult feeding and, where results were negative, by adult injection for the induction of sex‐linked recessive lethal mutations in meiotic and postmeiotic germ cell stages of Canton‐S males. One compound was tested by inhalation. Those compounds that induced lethal mutations were tested further for the induction of reciprocal translocations.Seventeen of the 53 compounds (acetaldehyde, 2‐aminoanthracene, bromoform, t‐butyl hydroperoxide, chlorambucil, trans‐cinnamaldehyde, crotonaldehyde, 1,3‐dichloro‐5,5‐dimethylhydantoin, 3,4‐dichloronitrobenzene, dimethoxane, 2,4‐dinitrotoluene, 1,2‐epoxy‐3,3,3‐trichloropropane, formaldehyde, furfural, halothane, HC yellow 4, and picric acid) were found to induce lethal mutations and three (2‐aminoanthracene, chlorambucil, and crotonaldehyde) also induced reciprocal translocations.
Antipain‐mediated suppression of sister chromatid exchanges induced by an inhibitor of poly (ADP‐ribose) polymerase
Authors: Schwartz Jeffrey L. , Weichselbaum Ralph R. 
Published: February 2007

AbstractExposure of mammalian cells to inhibitors of poly(ADP‐ribose) polymerase, such as 3‐aminobenzamide (3AB) results in the induction of sister chromatid exchanges (SCEs). The mechanism for the induction of SCEs by 3AB is unknown but is thought to be related to the incorporated halogenated pyrimidine used in SCE analysis. In this characteristic, 3AB‐mediated SCE induction is similar to the elevated SCE frequency found in Bloom's syndrome (BS) cells. Recently, it has been reported that certain protease inhibitors, such as antipain, will inhibit SCE induction in BS cells. We now report that antipain will also suppress 3AB‐induced SCE frequency. As has been reported for BS cells, the effects of antipain on SCE induction are partial, reducing SCE frequency by 0.15 to 0.40 SCE/chromosome (5–25% of the total induced frequency), and 30 μM concentrations of antipain are saturating. Antipain has no effect on baseline SCE frequency. These effects appear to involve free‐radical production because dimethylsulfoxide (DMSO), a free‐radical scavenger, will mimic the effects of antipain on 3AB‐induced SCEs. Both antipain and DMSO will also reduce the elevated SCE frequency found in cells exposed to high (100 μM or more) levels of bromodeoxyuridine (BrdUrd). High exogenous levels of BrdUrd produce some of the same biological effects as 3AB exposure. Thus, a minor fraction of the elevated SCE frequency seen in cells exposed to 3AB or to high levels of BrdUrd appears to be similar to that found in cultured BS cells and is probably due to some free‐radical‐producing process.