bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sister chromatid exchange in vivo in mice: I. The influence of increasing doses of bromodeoxyuridine
Authors: Wilmer James L. , Soares E. R. 
Published: February 2007

AbstractBromodeoxyuridine (BrdUrd) pellets weighing either 20, 25, 30, 35, 40, 45, or 53 mg were implanted subcutaneously in strain DBA/2J male mice. Femoral bone marrow cells were analyzed for sister chromatid exchange (SCE) and chromosome aberration frequencies, mitotic indices, and cellular replication kinetics. Small but statistically significant BrdUrd dose‐dependent increases of SCEs were observed, whereas chromosome aberrations were induced at low frequencies and occurred independently of BrdUrd dose. The mitotic index remained relatively constant for all doses. A slight inhibition of cellular replication, as manifested by a reduction in third division cells at the 40‐ and 45‐mg doses, was observed. The use of an intense fluorescent light source in the fluorescence‐plus‐Giemsa technique provided consistently good sister chromatid differentiation at pellet doses substantially lower than those previously used by other investigators.
Lack of an indication of mutagenic effects of dinitrotoluenes and diaminotoluenes in mice
Authors: Soares E. R. , Lock L. F. 
Published: February 2007

AbstractThe mutagenic effects of 2,4‐dinitrotoluene (2,4‐DNT), purified and technical grades, 3,5‐DNT, 2,4‐diaminotoluene (2,4‐DAT), and 2,5‐DAT were tested in mice using one or more of the following: the dominant lethal assay, the sperm morphology test and/or the recessive spot test. Compounds were administered by both intraperitoneal (IP) injection and gavage, and comparisons were made between controls and treated groups as well as between routes of administration. None of the five compounds tested produced a significant response in any of the systems employed. Treatment with purified 2,4‐DNT and 3,5‐DNT resulted in marked reductions in the percent of fertile matings. These data indicate a lack of mutagenicity of these compounds in the test systems employed here. The observed fertility effects are consistent with previously published data on DNT‐induced testicular damage.
The mutagenic effect of platinum compounds in drosophila melanogaster
Authors: Woodruff R. C. , Valencia R. , Lyman R. F. , Earle B. A. , Boyce J. T. 
Published: February 2007

AbstractThe platinum compounds cis‐platinum (II) diamminodichloride (cis‐PDD) (an anti‐tumor agent) and platinum tetrachloride (Pt Cl4) induce a significant increase in recessive sex‐linked lethal mutations in Drosophila melanogaster male germ cells in different developmental stages.
Enzyme mutants induced by low‐dose‐rate γ‐irradiation in drosophila: Frequency and characterization
Authors: Racine Robert R. , Langley Charles H. , Voelker Robert A. 
Published: February 2007

AbstractOne thousand lines of a balanced lethal strain of Drosophila melanogaster heterozygous at seven allozyme loci were subjected to chronic (0.15 rad/min) γ‐irradiation (137 Cs). After 15 generations of exposure they were screened by gel electrophoresis for newly arisen null mutants and/or mobility variants. Seven independent nulls were recovered. 1) None were associated with a cyto‐genetically detectable aberration; 2) one of six analyzed was associated with recessive lethality, suggesting association with a submicroscopic interlocus deficiency; 3) three of five which could be analyzed for cross‐reacting material (CRM) production were CRM‐positive; and 4) two of six produced an active heterodimer with an active normal allele. The results taken together suggest that most of the mutations are point mutations rather than small deficiencies.
Evidence that the repair deficient mei‐9a female in drosophila melanogaster is a strong potentiator of chromosome loss induced in the paternal genome by dimethyinitrosamine
Authors: Zimmering S. , Hartmann A. W. , Cooper S. F. 
Published: February 2007

AbstractFrom matings of Xc2/BsYy+ males treated or not with 2.5 mM DMN (dimethylnitrosamine) with repair‐deficient mei‐9a females or with ordinary females, induced frequencies of observed (recovered) chromosome loss were 3.69% and 0.65% and inferred (non‐recovered) ring‐X loss based on shifts in sex ratio (♀♀/♂♂) was 47.9% and 9.4%, respectively. Results indicate that the mei‐9a female is a strong potentiator of DMN‐induced chromosome damage in sperm and suggest that DMN‐induced chromosome lesions are produced in substantially higher frequency in treated sperm than deducible after crosses with repair‐efficient females.
The action of three anticlastogens on the induction of sister chromatid exchange by trenimon and 8‐hydroxyquinoline sulfate in human lymphocyte cultures
Authors: Gebhart E. , Kappauf H. 
Published: February 2007

AbstractThe influence of the anticlastogens β‐aminoethylisothiouronium (AET), d,1‐homocysteinethiolactone (HCT), and 1‐cysteine (CYS) on the frequency of sister chromatid exchanges (SCEs) induced by the chromosome damaging chemicals Trenimon and 8‐hydroxyquinoline sulfate (8‐HQS), was investigated in human lymphocyte cultures. None of the anticlastogens significantly influenced the SCE rate, whereas in the same or previous experiments the chromosome‐breaking effect of these clastogens was distinctly reduced by the anticlastogens. These results suggest that the sites of anticlastogenic activity do not coincide with the sites of SCE formation. SCE analysis, although it yields interesting and important information about the action of chemicals on genetic material, cannot replace classical aberration analysis, because the two parameters apparently reflect different patterns of molecular and cytogenetic activity of mutagens.
Variation in the baseline sister chromatid exchange frequency in human lymphocytes
Authors: Carrano A. V. , Minkler J. L. , Stetka D. G. , Moore D. H. 
Published: February 2007

AbstractThe utility of the sister chromatid exchange (SCE) assay for human population studies is potentially limited by the variability associated with individual baseline SCE frequencies. This investigation identifies and quantifies the major sources of preparative and biological variation associated with the determination of baseline SCE frequencies in cultured human lymphocytes. Much of the variation in lymphocyte SCE frequencies is attributable to the amount of bromodeoxyuridine (BrdUrd) available per lymphocyte; the pooled coefficient of variation (CV) over the dose range of 10 to 160 μM is about 18%. Other variations in the baseline frequency result from culture‐to‐culture and slide‐to‐slide differences. The pooled coefficient of variation among donors is about 10%. The effect of cell‐to‐cell differences in baseline SCE frequency among donors can be minimized by increasing the number of cells scored per donor. When 20 cells are analyzed per individual the pooled cell‐to‐cell variation is 9% but when 40 or 80 cells are analyzed it is reduced to 6 and 4% respectively. For a single individual the cell‐to‐cell coefficient of variation at 100 μM BrdUrd is 40.8%. Under our experimental conditions, a 30% increase in SCE frequency between two cohort populations can be detected with a 95% probability at a 5% level of significance when 11 individuals per cohort are studied. For a longitudinal or in vitro dose response study of a single individual, a 50% increase in SCE frequency can be detected with a 95% probability at a 5% level of significance when 25 cells per sample are analyzed. These results indicate the feasibility of applying the SCE bioassay to humans as a measure of environmental stress.
The anaerobe‐mediated mutagenicity of 2‐nitrofluorene and 2‐aminofluorene for salmonella typhimurium
Authors: Karpinsky George E. , Rosenkranz Herbert S. 
Published: February 2007

AbstractAnaerobic bacteria (Bacteroides fragilis, B vulgatus, and B thetaiotaomicron) possess the enzymic ability to convert 2‐nitrofluorene and 2‐aminofluorene to substances mutagenic for Salmonella typhimurium. If it be assumed that the active intermediate for both chemicals is 2‐hydroxylaminofluorene, then these bacteria possess reductive as well as oxidative capabilities.
Differential induction of sister chromatid exchanges by indirect‐acting mutagen‐carcinogens at early and late stages of embryonic development
Authors: Todd Lori A. , Bloom Stephen E. 
Published: February 2007

AbstractTo examine the development of drug‐metabolizing enzyme systems in the early chick embryo, the procarcinogens, aflatoxin B1 (AF‐B1) and 2‐acetylamino‐fluorene (2‐AAF), and the direct‐acting carcinogen, ethyl methanesulfonate (EMS) (positive control), were given to embryos; the sister‐chromatid‐exchange (SCE) technique was used as an indicator of conversion to active mutagenic metabolities. Chick embryos at two stages of incubation (3‐day and 6‐day) were exposed to the same graded series of dosages of the compounds for a period of 22 hours. All three mutagens increased the frequency of SCE above the control rate of 1.8 SCEs/cell. While a dose‐dependent increase in SCE was obtained for both procarcinogens at each age, the mean SCE frequency was significantly higher in the 6‐day embryos for each dosage given. In contrast, the direct‐acting mutagen, EMS, gave a reduced level of SCEs at the older age. These results suggest that the ability of early chick embryos to activate promutagens to forms capable of inducing SCE increases as development advances from three to six days of incubation (DI). In the 6‐day embryo, the metabolic conversion is enhanced, resulting in a significant increase in the mutagenicity of the test chemicals.
How many loci on the X‐chromosome of drosophila melanogaster can mutate to recessive lethals?
Authors: Abrahamson S. , Würgler F. E. , Dejongh C. , Meyer H. Unger 
Published: February 2007

AbstractThe sensitivity of the sex‐linked recessive lethal test is due to the fact that a very large number of loci are included in the mutation study. From extensive studies on the spontaneous sex‐linked recessive lethal frequency and spontaneous specific locus mutation rates, it is possible to derive an estimate of the number of loci included in the recessive lethal test. The average number derived from three estimates on male and female germ cells is 563 loci. A second independent approach derives from published data which analyzed short regions of the genome and the proportion of loci within these regions which mutate to lethality. This analysis suggests that 830 loci are potentially lethal mutables. We describe the reasons for concluding that 600 to 800 loci of the approximately 1,000 loci on the X‐chromosome are involved in the X‐linked recessive lethal test.
Short‐term cytogenetic assays of nine cancer chemotherapeutic drugs with metabolic activation
Authors: Au William W. , Johnston Dennis A. , Collie‐Bruyere Cheryl , Hsu T. C. 
Published: February 2007

AbstractNine anticancer drugs were analyzed in cell cultures with respect to their cytogenetic effects with or without the addition of liver fraction S9 as an in vitro metabolic system. Among them, vincristine was the only drug which induced a significant accumulation of mitosis with or without S9. Adriamycin and neocarzinostatin were most potent in induction of chromosome breakage, but their clastogenic activities were reduced after metabolic conversion. On the other hand, cyclophosphamide had a dose‐dependent activation of clastogenic effect by S9. The activity of bleomycin was enhanced by S9. S9 had no effect on the activities of actinomycin D, cytosine arabinoside, mitomycin C, and methotrexate. Vincristine showed no clastogenic property in our short‐term assay system with or without S9.The activities of these anticancer drugs observed from our assay were compatible with those from other assay systems. The incorporation of S9 or other metabolic systems in routine clastogen assays should allow us to improve our understanding of the genetic toxicity of chemical agents.
The relative contributions of B and T lymphocytes in the human peripheral blood mutagen test system as determined by cell survival, mitogenic stimulation, and induction of chromosome aberrations by radiation
Authors: Schwartz Jeffrey L. , Gautden Mary Esther 
Published: February 2007

AbstractFicoll‐Hypaque‐separated subpopulations of human peripheral blood T and B lymphocytes were exposed to 0, 0.5, 1.0, 2.5, or 5.0 Gy of γ rays. Three parameters were examined: Survival, as measured by trypan blue dye exclusion in unstimulated cultures five days after irradiation; mitotic index, measured in phytohemagglutinin (PHA)‐stimulated cultures 48 and 72 hours after irradiation; and chromosome aberration frequency, measured 48 or 60 hours after irradiation.Survival curves of T, B, and null cells are biphasic; the D0 values for the radiosensitive populations of all three cell types are close to 0.6 Gy but are different for the radioresistant populations: 2.7 Gy for B cells, 4.77 Gy for T cells, and 6.03 Gy for null cells. B cells, as well as T cells, are stimulated to divide by PHA, and B cells comprise at least 10% of the mitotic figures seen in unirradiated cultures at 48 hours. The proportion of B lymphocytes in mitosis at any particular time after PHA stimulation decreases with increasing radiation dose, which reflects a higher mitotic radiosensitivity of B than of T cells. No significant difference, however, in chromosome aberration frequency was found between T and B cells.
Potentiation of chromosome loss induced in the paternal genome by methyl methanesulfonate and procarbazine following matings with repair deficient mei‐9a females of drosophila
Authors: Zimmering S. , Kammermeyer K. L. 
Published: February 2007

AbstractDrosophila melanogaster males carrying a ring‐X (Xc2) and a doubly‐marked Y chromosome (BSYy+) were treated with methylmethane sulfonate (MMS) and procarbazine, and mated with repair‐deficient mei‐9a females or ordinary repair‐proficient females. Observed (recovered) chromosome loss were scored and nonrecovered inferred. Ring‐X loss based on shifts in sex ratio were noted. Results indicate that the mei‐9a female is a strong potentiator of chromosome loss induced by MMS and procarbazine in line with the effect recently shown for dimethylnitrosamine (DMN)‐induced chromosome lesions (Zimmering, et al 1980.
A maternal effect in homozygous mei‐9amei‐41D5 repair deficient drosophila melanogaster females influencing the recovery rate of progeny bearing a Y chromosome
Authors: Zimmering S. , Cooper S. F. 
Published: February 2007

AbstractEvidence is presented supporting the suggestion that homozygosity for the repair‐deficient mutants mei‐9a mei‐41D5 is associated with a maternal effect which affects detrimentally the recovery rate of Y chromosome‐bearing offspring.
Sensitivity of drosophila melanogaster to low concentrations of gaseous mutagens: III. Dose‐rate effects
Authors: Kale P. G. , Baum J. W. 
Published: February 2007

AbstractSex‐linked recessive lethal mutations were induced in D melanogaster males by chronic as well as acute treatments of gaseous 1, 2‐dibromoethane ranging from 2.3 to 31 ppm.hr. Acute treatments corresponding to each chronic treatment were made by increasing chemical concentration approximately 30 times with a concomittant decrease in exposure period. Germ cell stages sampled, in order of decreasing sensitivity, were spermatocytes, spermatids, and spermatozoa. The most significant finding is that no consistent pattern of difference is observed between acute and chronic exposure for three of the four exposure levels. Only at the highest exposure level (30–31 ppm.hr) was any consistent difference observed between chronic and acute exposure levels. At the higher exposure level in all three germ cell stages the acute exposure showed a significant increase in mutation frequency over the chronic exposure. The greater acute vs chronic mutation frequency for spermatozoa, a metabolically inactive cell stage, leads to the conclusion that the exposure rate effect at high exposure levels is due to systemic factors such as metabolic deactivation or elimination rather than repair of premutational damage in the target cells. The significance of these observations in risk assessment for environmental pollutants is discussed.
Metabolic activation of carcinogens in the salmonella mutagenicity assay by hamster and rat liver S‐9 preparations
Authors: Raineri Ronald , Poiley Judith A. , Pienta Roman J. , Andrews A. W. 
Published: February 2007

AbstractBefore exerting a carcinogenic or mutagenic effect, many carcinogens must undergo metabolic activation. Liver S‐9 preparations from rats treated with Aroclor 1254 (AC) have been widely used to extend the ability of the Salmonella mutagenicity assay to detect such nondirect‐acting agents. We compared the mutagen‐activating capabilities of liver S‐9 preparations from both Syrian golden hamsters and Sprague‐Dawley rats. The comparison was made between S‐9 fractions from untreated, and phenobarbital (PB)‐ and AC‐treated animals of both sexes. Also compared was the effect of varying the amount of S‐9 protein. The preparations from hamster liver were consistently more effective than preparations from rat liver for the activation of 2‐acetylaminofluorene (AAF), 2‐aminoanthracene (AA) (except for AC‐induced preparations), 3‐methylcholanthrene (MCA), and diethylnitrosamine (DEN) to their mutagenic forms. Induced preparations from rats were more active than those from hamsters when using benzo(a)pyrene (BP), while with uninduced preparations, the opposite was true.There was also a relationship between the amount of S‐9 protein and the number of revertant colonies obtained. With the aromatic amines (AAF and AA), a partial inhibition of mutagenicity occurred at the highest protein concentrations tested. With BP, an inverse relationship was observed between protein concentration and the number of revertants occurring in the presence of the preparation from PB‐ and AC‐induced male and female rats.The relative order of activities of aryl hydrocarbon hydroxylase (AHH) and BP‐4,5‐epoxide hydrase (EH) in the preparations was AC‐induced > PB‐.
A standardized procedure for quantification of the ames salmonella/mammalian‐microsome mutagenicity test
Authors: Belser William L. , Shaffer Steven D. , Bliss Richard D. , Hynds Paul M. , Yamamoto Lynn , Pitts James N. , Winer Judy A. 
Published: February 2007

AbstractFactors determining the precision and variability of the Ames Salmonella test for mutagenicity were investigated. The most important source of variability in the agar‐overlay method was nonuniformity in the soft‐agar layer thickness. Solution of this problem resulted from application of an agar‐leveling table described in this paper. Several other procedural elements also contribute to improved precision, including temperature uniformity during incubation, incubation interval, consistency of plate agar volume, completeness of mixing the soft‐agar overlay, peculiarities in the interaction of mutagens and mammalian liver microsomal extract (S9), and methods of storage and controls for tester strains. When these and other effects were well‐controlled, variability of the test results was reduced from 200 or 300% to only ± 10% or less. The significance of the factors affecting precision are discussed and an improved experimental protocol is presented.
Stability of activating systems for in vitro mutagenesis assays: Enzyme activity and activating ability following long‐term storage at ‐ 85°c
Authors: Dent John G. , Schnell Stephanie , Graichen M. Elizabeth , Allen Paula , Abernethy Diane , Couch David B. 
Published: February 2007

AbstractActivating systems for in vitro mutagenesis assays are commonly prepared and stored at low temperature until required. The objective of the studies reported here was to determine the long‐term stability of activating systems stored at ‐ 85°C. A broad range of microsomal enzymes in the postmitochondrial supernatant (PMS) and the microsomal fraction of livers from Aroclor 1254 treated rats were studied in conjunction with the ability of these fractions to catalyse the conversion of dimethylnitrosamine (DMN) and benzo(a)pyrene (B(a)P) to products mutagenic to Chinese hamster ovary (CHO) cells and Salmonella typhimurium TM677. Biphenyl‐2‐ and biphyeny 1‐4‐hydroxylase showed a rapid decline in activity on storage, epoxide hydratase activity increased with storage and other enzyme activities studied were relatively stable for up to 32 weeks. No consistent trends in the ability of either the microsomes or the PMS to catalyze DMN or B(a)P induced mutation were observed for up to 12 weeks with CHO cells and 24 weeks with bacteria. It is concluded that low temperature storage of activating systems is an acceptable procedure. However, the results also indicate that certain enzyme activities change during storage, suggesting that aberrant results may be obtained when stored activiating systems are used in in vitro tests to screen for mutagens.
Mutagenicities of 61 flavonoids and 11 related compounds
Authors: Nagao Minako , Morita Naokata , Yahagi Takie , Shimizu Mineo , Kuroyanagi Masanori , Fukuoka Masamichi , Yoshihira Kunitoshi , Natori Shinsaku , Fujino Tadahiko , Sugimura Takashi 
Published: February 2007

AbstractThe mutagenicities of 61 flavonoids (naturally occurring flavonoid aglycones and flavonal glycosides and synthetic flavonoids) and those of 11 compounds structurally related to flavonoids were tested with Salmonella typhimurium strains TA100 and TA98. Among the 22 flavone derivatives tested, only wogonin was strongly mutagenic, while five derivatives, apigenin triacetate, acacetin, chrysoeriol, pedalitin, and pedalitin tetraacetate, were only weakly mutagenic. Two bisflavonyl derivatives, neither of which has a 3‐hydroxyl group, were not mutagenic. Of the 16 flavonol derivatives tested, all except 3‐hydroxyflavone and the tetra‐ and penta‐methyl ethers of quercetin were mutagenic. Of the five flavanone derivatives tested, only 7,4‐dihydroxyflavanone was mutagenic, showing weak activity. Of the four flavanonol derivatives tested, hydrorobinetin and taxifolin were weakly mutagenic. Of the six isoflavone derivatives tested, tectorigenin was weakly mutagenic. Of the 11 compounds in the miscellaneous group structurally related to flavonoids, only iso‐liquiritigenin was mutagenic, showing weak activity. For the emergence of strong mutagenicity, the double bond between positions 2 and 3 and the hydroxyl group at position 3 are required, except in wogonin, which does not have a hydroxyl group at position 3 but is strongly mutagenic to TA100. The 3‐O‐acetyl ester of flavonol, quercetin, was mutagenic with S9 mix, but 3‐O‐methyl ethers were not. Six flavonol glycosides, three quercetin glycosides and three kaempferol glycosides were mutagenic after preincubation with “hesperidinase,” a crude extract of Aspergillus niger. Of 66 flavonoid agylcones and compounds structurally related to flavonoids, quercetin was the strongest mutagen. The carcinogenicity of this compound should be clarified because it is ubiquitously found in vegetables.
Evidence for the existence of a family of bacterial nitroreductases capable of activating nitrated polycyclics to mutagens
Authors: McCoy Elena C. , Rosenkranz Herbert S. , Mermelstein Robert 
Published: February 2007

AbstractA derivative of Salmonella typhimurium TA98 which does not respond to the potent mutagenicity of 1,8‐dinitropyrene is described. This novel strain also shows a lack of response to the mutagenic action of 1,3‐dinitropyrene and a greatly reduced response to 1,6‐dinitropyrene and 1‐nitropyrene. The responses to 1,3,6‐trinitropyrene and 1,3,6,8‐tetranitropyrene are affected to a much lesser extent. This strain (TA98/1,8DNP6) is fully sensitive to the mutagenicity of 4‐nitroquinoline‐1‐oxide, niridazole, nitroacridine, and nonnitrated frameshift mutagens. This strain appears to be deficient in a nitroreductase which reduces nitrated pyrenes and possibly other nitrated polycyclic aromatic hydrocarbons to corresponding hydroxylamines, the penultimate mutagens.