bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acrylamide exposure induces a delayed unscheduled dna synthesis in germ cells of male mice that is correlated with the temporal pattern of adduct formation in testis DNA
Authors: Sega Gary A. , Generoso Estela E. , Brimer Patricia A. , Malling H. V. 
Published: February 2007

AbstractA study of meiotic and postmeiotic germ‐cell‐stage sensitivity of male mice to induction of unscheduled DNA synthesis (UDS) by acrylamide showed that DNA repair could be detected in early spermatocytes (after the last scheduled DNA synthesis) through about mid‐spermatid stages. No DNA repair could be detected in later stages. The maximum UDS response was observed 6 hr after i.p. exposure and was about 5 times greater than the response measured immediately after treatment. This is the longest delay between chemical treatment and maximum UDS response yet observed in mouse germ cells. There was a linear relationship between the UDS response and acrylamide exposure from 7.8 to 125 mg/kg.By using 14C‐labeled acrylamide it was determined that the temporal pattern of adduct formation in testes DNA paralleled that of the UDS response, with maximum binding occurring 4 to 6 hr after exposure. In contrast, the temporal pattern of adduct formation in liver DNA showed maximum binding within 1 to 2 hr after exposure and was an order of magnitude greater than that found for the testis DNA.
Significant differences in the structural basis of the induction of sister chromatid exchanges and chromosomal aberrations in chinese hamster ovary cells
Authors: Rosenkranz Herbert S. , Ennever Fanny K. , Dimayuga Mario , Klopman Gilles , Hoiden H. E. 
Published: February 2007

AbstractThe structural basis of the induction of sister chromatid exchanges (SCE) and chromosomal aberrations (Cvt) in Chinese hamster ovary cells was investigated by the CASE (Computer Automated Structure Evaluation) method, on artificial‐intelligence‐based system. Using the relevant National Toxicology Program data bases CASE identified a set of structural determinants responsible for the induction of SCE and another one for Cvt.A comparison between the structural determinants associated with SCE and Cvt revealed an overlap of only 22.6%, while the overlap between SCE and the determinants of mufagenicity in Salmonella is 54.5%. This indicates a) that the structural bases of the two phenomena differ and b) that it is likely that SCE, but not Cvt, involves a significant electrophilic/DNA‐damaging component.
Comparison of radon‐daughter‐induced effects in repair‐proficient and repair‐deficient cho cell lines
Authors: Snyder R. D. , Schwartz Jeffrey L. , Shadley Jeff D. , Atcher Robert W. , Tang Jian , Whitlock Jenny Lee , Rotmensch Jacob 
Published: February 2007

AbstractThe radiobiological effects of the radon daughter 212Bi were investigated in the Chinese hamster ovary cell line AA8 and its radiosensitive derivative EM9. EM9 cells rejoin radiation‐induced DNA strand breaks more slowly than do AA8 cells. Three endpoints were examined: cell killing, G2‐induced chromosome aberration frequency, and mutation induction at the hypoxanthine (guanine) phosphoribosyltransferase (HGPRT) locus. Cells were exposed to the alpha‐emitter 212Bi chelated to diethylenetriaminepentaacetic acid (212Bi‐DTPA). As expected, 212Bi‐DTPA was more effective than X‐rays in producing cytotoxicity, chromosome aberrations, and gene mutations. The relative biological effectiveness (RBE) for all three endpoints ranged from about 2 for chromosome aberrations to 4.4 for mutation induction. EM9 was more sensitive than AA8 cells to the cytotoxic and clastogenic effects of both X‐rays and 212Bi‐DTPA, suggesting that the repair deficiency in EM9 cells affects response to low‐and high‐linear energy transfer (LET) radiation for these endpoints. There was no significant difference between these two cell lines in their mutagenic response to X‐rays and AA8 was slightly more sensitive to the mutagenic effects of alpha radiation. These results suggest that alterations in DNA repair ability may affect response of cells to both low‐ and high‐LET radiation‐induced cytotoxicity and clastogenicity, but they appear to have little effect on gene mutation induction.
Mutagenesis assays on urines produced by patients administered adriamycin and cyclophosphamide
Authors: Newman M. A. , Que Hee S. S. , Schoeny R. S. 
Published: February 2007

AbstractThe XAD‐2 resin concentration/elution system for concentration of mutagens contained in urines was optimized for cancer patients who had been administered such antineoplastic agents as adriamycin (ADR; doxorubicin), cyclophosphamide (CP), methotrexate, vincristine, and 5‐fluorouracil. In the reverse mutation assay, Salmonella typhimurium strains TA1535 and TA98 differentiated between CP (with S9 fraction) and ADR (without S9), respectively. No dose‐response for CP was observed. There was a dose‐response to ADR by TM677 in the presence of S9 using a forward mutation assay. However, while the reverse mutation assays successfully detected ADR and CP administration in the presence of each other in terms of urine mutagenicity, the forward mutation assay did not, since unidentified CP metabolites were also detected in the latter. None of these systems detected mutagenic urines from tobacco smokers, although reaction of these urines with β‐glucuronidase allowed this type of source to be detected also.
Aneuploidy in drosophila. III: Aneuploidogens inhibit in vitro assembly of taxol‐purified drosophila microtubules
Authors: Sehgal A. , Osgood C. , Zimmering S. , Aaron C. S. 
Published: February 2007

AbstractThe in vitro effects of aneuploidogens on taxolpurified microtubules from whole Drosophila melanogaster and mouse brain were studied by a spectrophotometric assay and electron microscopy. Colchicine, acetonitrile, propionitrile, acrylonitrile, dimethylsulfoxide (DMSO), griseofulvin, and cadmium chloride inhibit microtubule assembly, whereas methoxyethyl acetate (MEA) does not. Qualitatively similar results were observed with D. melanogoster and mouse brain microtubules. The in vitro results from D. melanogaster correlate well with previously published results from in vivo assays monitoring induced sex chromosome aneuploidy in that effective aneuploidogens are observed to affect microtubule assembly. The inclusion of taxol does not appear to qualitatively affect the assembly assays with the chemicals tested. In contrast with results from assembly assays, the tested aneuploidogens, including colchicine, do not promote disassembly to taxol‐purified microtubules. It is possible that taxol has shifted the equilibrium and stabilized the formed microtubules to the extent that they are no longer sensitive to aneuploidogen‐induced disassembly.
Metabolism and bacterial mutagenicity of binary mixtures of benzo(a)pyrene and polychlorinated aromatic hydrocarbons
Authors: Donnelly K. C. , Brown K. W. , Anderson C. S. , Barbee G. C. , Safe S. H. , Mortlemans K. E. 
Published: February 2007

AbstractThe results of both the Salmonella/microsome mutagenicity assay and high‐performance liquid chromatography (HPLC) analysis were used to evaluate the interactions of binary mixtures of benzo(a)pyrene (BAP) and several different polychlorinated aromatic hydrocarbons. Binary mixtures of either 2‐nitro‐3,7,8‐trichlorodibenzo‐p‐dioxin (2NTCDD) or pentachlorophenol (PCP) with BAP produced synergism, whereas strictly additive effects were observed with mixtures of acta‐ or hepta‐chlorodibenzo‐p‐dioxin and BAP. At a dose of 50 μg per plate, BAP induced 120 total revertants, whereas the binary mixture of BAP and PCP induced 303 total revertants. The binary mixture of BAP at 1 μg per plate and 2NTCDD at 0.5 μg per plate induced 261 net revertants, whereas BAP alone induced 42 net revertants. HPLC analysis of the mixtures indicated that preincubation of BAP with 2NTCDD increased the quantity of benzo(a)pyrene‐7,8‐dihydrodiol, and 9,10‐dihydrodiol metabolites detected. The data suggest that nonmutagenic components of a complex mixture may alter the metabolism of promixate mutagens. Thus, in the present study, 2NTCDD appears to have inhibited the detoxication of BAP metabolites.
In vitro and in vivo genotoxicity evaluation of hormonal drugs. I. Hydrocortisone
Authors: Bali Deeksha , Singh Jai Rup , Singh Harbhajan , Sandhu Dharambir , Reidy J. A. 
Published: February 2007

AbstractGenotoxic evaluation of a widely used glucocorticoid, hydrocortisone, was undertaken using a battery of in vitro and in vivo test systems. Human lymphocyte cultures and mouse bone marrow studies (micronuclei and sister chromatid exchange analyses) showed the drug to be very potent clastogen. However, the Ames/Salmonella assay both with and without S9 did not show an increase in the His+ revertants.
Morphological transformation of BALB/3T3 cells by various procarcinogens in the presence of a rat liver S‐9 activation system
Authors: McCarvill John T. , Lubet Ronald A. , Schechtman Leonard M. , Kouri Richard E. , Putman Donald L. 
Published: February 2007

AbstractAn Aroclor‐induced rat hepatic S‐9 metabolic activation system was incorporated into the BALB/3T3 cell transformation assay to increase its sensitivity to a wide range of procarcinogens. S‐9 was prepared from Aroclor 1254‐induced (500 mg/kg) Fischer 344 rats. Cyclophosphamide, dimethylnitrosamine, 2‐aminofluorene, and 2‐naphthylamine were metabolized to reactive forms capable of inducing both dose‐dependent toxicity and morphological transformation of BALB/3T3 cells. Treatments without an exogenous metabolic activation system were nontoxic and nontransforming. Adaptation of this commonly used exogenous metabolic activation system to BALB/3T3 cells will allow detection of the transforming potential of procarcinogens which test negative in a standard assay.
Development of an optimal S9 activation mixture for the L5178Y TK+/− mouse lymphoma mutation assay
Authors: Majeska Jenness B. , Matheson Dale W. , Holden H. E. 
Published: February 2007

AbstractIn previously described activation systems [Clive D, Spector JFS (1975): Mutat Res 31:17—29] for the mouse lymphoma mutation assay the cofactor isocitrate is rapidly exhausted and the resultant loss of NADPH can halt metabolic processes. Presented here are data obtained with a non‐toxic balance of NADP (1.4 mg/ml), isocitrate (6.0 mg/ml), and S9 (≤4%) in Fischer's medium which produces a more stable supply of the required cofactors. By spectrophotometric analysis, the molar concentration of NADPH remains at ≥50% or more of the maximum over the usual 4‐hr treatment period. Accompanying this increase in NADPH duration was increased toxicity and mutant frequency at most doses among cells treated with the reference mutagens 3‐methylcholanthrene (MCA), 2‐acetylamofluorene (AAF), benzo(a)pyrene(BAP),9,10‐dimethyl‐1,2‐benzanthracene (DMBA), or cyclophosphamide (CPA), but not with dimethylnitrosamine (DMN)‐possibly a reflection of the single enzyme mediated step in the metabolism of this chemical. These observations also suggest that results attributed to varying the amounts of S9 in an activation mixture may be due to suboptimal cofactor levels and further emphasize the need to maintain sufficient NADPH exposure to evaluate the effects of metabolic enzyme levels or compare the relative activities of analogous chemicals.
Use of the spiral salmonella assay to detect the mutagenicity of complex environmental mixtures
Authors: Houk Virginia Stewart , Claxton Larry D. , Early Gloria , Morgan R. W. 
Published: February 2007

AbstractThe success demonstrated by the spiral Salmonella assay in a recent study of 20 pure prompted us to examine the effectiveness of this automated bacterial mutagenicity assay for testing complex environmental mixtures. Three sets of combustion emissions were selected for evaluation: automotive diesel exhaust, woodsmoke, and a coal combustion emission. Each sample was tested in the Salmonella mutagenicity assay according to standard protocol (plate incorporation) and spiral assay techniques. In the spiral assay, a specialized plating instrument dispenses the bacteria, test agent, and S9 mix in a spiral pattern onto a minimal agar plate supplemented with histidine and biotin. The components of the assay are administered in such a way that a uniform density of bacteria is exposed to a concentration gradient of the test agent on a single plate. When results are analyzed, a dose‐response curve comprised of 13 data points is generated. A comparison of results from the two assays demonstrated the following: 1) Diesel exhaust was generally the most mutagenically potent sample in both assays, followed closely by the coal combustion emission. The woodsmoke sample was only weakly mutagenic in the standard assay but demonstrated higher mutagenic activity in the spiral assay. 2) Samples were more mutagenic on rev/μg basis in the spiral assay, especially when metabolic activation was added. This disparity presumably was due to differences in the relative amounts of S9 administered across the dose range. 3) The spiral assay required 1/20 the sample mass of the standard assay to test equivalent doses; in addition, for some samples, 50 times more sample mass was required by the standard assay to generate a comparable dose response. 4) Dichloromethane extracts of the complex mixtures could be tested for mutagenicity in the spiral assay, thereby precluding solvent exchange (to dimethylsulfoxide) required by the standard assay for sample/bioassay compatibility.
Comparative mutagenicity of nitrofluoranthenes in salmonella typhimurium TA98, TA98NR, and TA98/1,8DNP6
Authors: Shane B. S. , Squadrito G. L. , Church D. F. , Pryor W. A. , MacPhee D. G. 
Published: February 2007

AbstractThe nitration of fluoranthene, one of the most abundant polycyclic aromatic hydrocarbons (PAH) in diesel fuels, occurs in the laboratory under either electrophilic or free‐radical conditions to give nitro‐PAH. 3‐Nitrofluoranthene (3‐NF) is the major product under electrophilic ionic conditions while 2‐nitrofluoranthene (2‐NF) is the major product under free‐radical nitration conditions. The free‐radical nitration of fluoranthene also yields 1,2‐ and 1,3‐dinitrofluoranthene (1,2‐DNF and 1,3‐DNF).Nitration on the 3‐position of fluoranthene enhances the mutagenic potency more strongly than on the 2‐position. Thus, 3‐NF is a more potent mutagen than 2‐NF and 1,3‐DNF is more potent than 1,2‐DNF, an isomer with one near coplanar nitro group and one nitro group substantially out of plane with the fluoranthene skeleton, when tested against Salmonella typhimurium TA98, TA98NR, and TA98/1,8‐DNP6. In addition, the activation of these dinitro‐PAH to mutagens does not depend on the “classical nitroreductase” and/or O‐acetylase, suggesting that they are activated via different pathways. Despite the fact that 3‐NF and 1‐phenyl‐4‐nitronaphthalene (1‐P‐4NN), a non‐planar analog of 3‐NF, have virtually identical reduction potentials, their mutagenic potencies differ by three orders of magnitude. This finding suggests that when nitro‐PAH of varying steric requirements are compared, the reduction potential may not predict mutagenic potency as well as had been previously suggested.
Nitro group orientation, reduction potential, and direct‐acting mutagenicity of nitro‐polycyclic aromatic hydrocarbons
Authors: Jung Hyewook , Heflich Robert H. , Fu Peter P. , Shaikh Ali U. , Hartman P. E. 
Published: February 2007

AbstractNitro‐polycyclic aromatic hydrocarbons (nitro‐PAHs) are widespread genotoxic environmental pollutants. We have been interested in determining the structural and electronic features that may be useful in predicting the direct‐acting mutagenic activity of nitro‐PAHs in Salmonella typhimurium. In this study, a series of structurally related nitro‐PAHs were used to determine the relationships among direct‐acting mutagenicity, orientation of the nitro group, and reduction potential of the nitro group. The compounds consisted of isomeric mononitrated and dinitrated benzo[e]pyrenes, their derivatives, and other nitro‐PAHs ranging from two to five aromatic‐ring molecules in size. A general finding is that nitro‐PAHs with their nitro substituent oriented perpendicular to the aromatic system exhibit either very weak or no direct‐acting mutagenicity in S. typhimurium strains TA98 and TA100. However, if a nitro‐PAH of this type has a relatively low first half‐wave reduction potential, it may be direct‐acting. Furthermore, a positive correlation between the first half‐wave reduction potential and direct‐acting mutagenicity is found only when the compounds are structurally similar. Consequently, the correlation cannot be made using nitro‐PAHs with different molecular size. Nitro‐PAHs having a perpendicular nitro orientation always have a higher (absolute value) first half‐wave reduction potential than the isomer(s) with a parallel orientation. Perhaps due to electron‐withdrawing by the second nitro group, dinitro‐PAHs always have a lower first half‐wave reduction potential than their mononitro analogues. These findings provide a useful molecular basis for interpreting and predicting the direct‐acting mutagenicity of nitro‐PAHs.
In vivo somatic mutation in the lymphocytes of Hodgkin's disease patients
Authors: Caggana Michele , Liber Howard L. , Mauch Peter M. , Coleman C. Norman , Kelsey Karl T. , O'Neill J. P. 
Published: February 2007

AbstractWhile current medical therapies for Hodgkin's disease are usually quite effective, it has become increasingly clear that some of the therapies utilized carry an inherent risk for the induction of secondary malignancies. In order to examine the cellular and genetic responses to therapy for Hodgkin's disease among individuals, we have determined the mutant frequency of T‐lymphocytes in 3 cohorts of patients (N = 86) and in controls (N = 71) using a T‐cell cloning assay selecting for 6‐thioguanine resistance. The Hodgkin's disease cohorts studied include 1) new and untreated, 2) radiotherapy, and 3) combined modality therapy patients. Additionally, two patients receiving chemotherapy alone were studied. In untreated patients, 3 of 18 (17%) mutant frequencies were above the upper 95% confidence limit for mutant frequency in controls (12.6 × 10−6). After therapy, 14 out of 45 (31%) of those treated with X‐rays only and 10 of 23 (44%) patients treated with both X‐rays and chemotherapy had mutant frequencies greater than 12.6 × 10−6. Overall, the results indicated that the individual response to Hodgkin's disease therapy was a heterogeneous one with a sub‐population of persons having elevated mutant frequencies even many years after their last treatment. The larger frequency of elevated MFs in those patients who received intensive therapy (chemotherapy and radiotherapy) is consistent with their increased risk for second cancer induction.
Characterization of a method for quantitating food consumption for mutation assays in Drosophila
Authors: Thompson E. D. , Reeder B. A. , Bruce R. D. , Lee W. R. 
Published: February 2007

AbstractQuantitation of food consumption is necessary when determining mutation responses to multiple chemical exposures in the sex‐linked recessive lethal assay in Drosophila. One method proposed for quantitating food consumption by Drosophila is to measure the incorporation of 14C‐leucine into the flies during the feeding period (Thompson and Reeder: Environmental Mutagenesis 10:357–365, 1987). Three sources of variation in the technique of Thompson and Reeder have been identified and characterized. First, the amount of food consumed by individual flies differed by almost 30% in a 24 hr feeding period. Second, the variability from vial to vial (each containing multiple flies) was around 15%. Finally, the amount of food consumed in identical feeding experiments performed over the course of 1 year varied nearly 2‐fold. The use of chemical consumption values in place of exposure levels provided a better means of expressing the combined mutagenic response. In addition, the kinetics of food consumption over a 3 day feeding period for exposures to cyclophosphamide which produce lethality were compared to non‐lethal exposures. Extensive characterization of lethality induced by exposures to cyclophosphamide demonstrate that the lethality is most likely due to starvation, not chemical toxicity.
Evaluation of the mutagenicity of β‐myrcene in mammalian cells in vitro
Authors: Kauderer Barbara , Zamith Helena , Paumgartten Francisco J. R. , Speit Günter , Holden H. E. 
Published: February 2007

AbstractThe genotoxicity of the terpene β‐myrcene was evaluated in mammalian cells in vitro. Myrcene is the major constituent of oil of bay and hop which are used in the manufacture of alcoholic beverages. Myrcene is also present in lemon grass (Cymbopogon citratus), a plant widely used in Brazilian folk medicine. Recently, it was shown that myrcene is a very potent analgesic substance and might be an alternative to the already available analgesic drugs. Myrcene was tested up to 1,000 μg/ml (limit of solubility) in the presence and absence of S9‐mix and did not induce chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes in vitro. Neither the mitotic index nor the proliferation index was influenced by the myrcene treatment. Myrcene did not cause increased mutation frequencies at the hprt‐locus in V79‐cells. Tests with and without S9‐mix revealed negative results. There was no indication for induced cytotoxicity. However, myrcene reduced the SCE‐inducing effect of cyclophosphamide in human lymphocytes in a dose dependent manner and also reduced the toxic and mutagenic effect of cyclophosphamide in V79‐cells. Under the same test conditions, SCE induction by ethyl methanesulfonate (EMS) and benzo [a]pyrene (BP) was not significantly influenced by simultaneous myrcene treatment. The in vitro results show that myrcene is not mutagenic in mammalian cells, but has antimutagenic properties. The possibility that myrcene exerts its antimutagenic activity by inhibiting certain forms of the cytochrome P‐450 isoenzymes required for activation of premutagens and precarcinogenes is discussed.
Effect of pentachlorophenol on the activation of 2,6‐dinitrotoluene to genotoxic urinary metabolites in CD‐1 mice: A comparison of GI enzyme activities and urine mutagenicity
Authors: George S. Elizabeth , Chadwick Robert W. , Creason John P. , Kohan Michael J. , Dekker John P. , O'Neill J. P. 
Published: February 2007

Abstract2,6‐Dinitrotoluene (2,6‐DNT) and pentachlorophenol (PCP) are used for industrial purposes and are found in the environment as hazardous contaminants. Because concurrent exposure to both compounds can occur, it is of interest to determine if organochlorine compounds potentiate the effect of nitroaromatic chemicals. CD‐1 mice were treated with PCP (42.8 mg/kg) for 4 weeks. On weeks 1,2, and 4 after the initial PCP dose, mice were treated p.o. with 2,6‐DNT (75 mg/kg) and 24 hr urines were collected. After concentration, the urines were tested for their mutagenic activity in Salmonella typhimurium strain TA98 without metabolic activation in a microsuspension bioassay. A significant increase (P < .05) in mutagenicity was observed in urines from mice treated with 2,6‐DNT alone and in combination with PCP. By week 4, mice that received both 2,6‐DNT and PCP excreted urine that was more mutagenic than that from animals which received only 2,6‐DNT. At weeks 2 and 4, mice were sacrificed and intestinal enzyme activities (nitroreductase, azo reductase, β‐glucuronidase, dechlorinase, and dehydrochlorinase) were quantitated. The enhanced genotoxicity observed in urines from 2,6‐DNT/PCP‐treated mice coincided with a decrease in nitroreductase and an increase in β‐glucuronidase activities in the small intestine.