Environmental and Molecular MutagenesisThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

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411 records returned

Genotoxicity of a freshwater cyanotoxin, cylindrospermopsin, in two human cell lines: Caco-2 and HepaRGEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cylindrospermopsin (CYN), a cyanotoxin produced by certain freshwater cyanobacteria, causes human intoxications and animal mortalities. CYN is a potent inhibitor of protein- and glutathione-synthesis. Preliminary evidence for in vivo tumor initiation has been found in mice but the mechanism remains unclear. Several in vitro and in vivo studies demonstrate that CYN is genotoxic and requires metabolic activation. In the present study, the genotoxicity of CYN was assessed in human hepatocyte and enterocyte cell lines, which are models for CYN target organs. The cytokinesis-block micronucleus assay was conducted on liver-deriv...
Source: Environmental and Molecular Mutagenesis - November 10, 2009 Category: Molecular Biology Authors: Emmanuelle Bazin, Annick Mourot, Andrew R. Humpage, Valérie Fessard Source Type: journals

Effect of O6-chloroethylguanine DNA lesions on the kinetics and mechanism of micronucleus induction in vivoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined groups of five mice treated with (i) dimethylsulfoxide (DMSO), (ii) O6BG in DMSO, (iii) BCNU, or (iv) O6BG in DMSO plus BCNU. The data indicate that O6BG pretreatment causes: (i) ían increase in MN-PCEs induced by BCNU, (ii) a delay in the time of maximal MN-PCE induction produced by the different BCNU doses, and (iii) an increase in cytotoxicity. These data confirm that O6-ChlEt-G is a lesion involved in DNA break induction and in the subsequent production of micronuclei, and also that these lesions seem to be stoichiometrically reduced by MGMT. These data also show that induction of MN-PCEs by BCNU is delaye...
Source: Environmental and Molecular Mutagenesis - October 20, 2009 Category: Molecular Biology Authors: P. Morales-Ramírez, T. Vallarino-Kelly, V.L. Cruz-Vallejo Source Type: journals

Excretion characteristics of urinary 8-hydroxydeoxyguanosine after dietary exposure to polycyclic aromatic hydrocarbonsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Urinary 8-hydroxydeoxyguanosine (8-OHdG) is considered a noninvasive marker for oxidative stress and also a marker of carcinogenic potential for compounds such as polycyclic aromatic hydrocarbons (PAHs). Although human studies have investigated urinary 8-OHdG concentrations in PAH-exposed workers and the general population, the background level and excretion kinetics of urinary 8-OHdG in humans remain unclear. Two feeding experiments (consumption of barbecued meat of 15 and 30 g/kg for Experiments 1 and 2, respectively) were conducted to examine the excretion characteristics of urinary 8-OHdG. All urine voided over 7 days ...
Source: Environmental and Molecular Mutagenesis - October 19, 2009 Category: Molecular Biology Authors: Yeh-Chung Chien, Chun-Ting Yeh Source Type: journals

DNA damage and oxidative stress in human liver cell L-02 caused by surface water extracts during drinking water treatment in a waterworks in ChinaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Because of the daily and life-long exposure to disinfection by-products formed during drinking water treatment, potential adverse human health risk of drinking water disinfection is of great concern. Toxicological studies have shown that drinking water treatment increases the genotoxicity of surface water. Drinking water treatment is comprised of different potabilization steps, which greatly influence the levels of genotoxic products in the surface water and thus may alter the toxicity and genotoxicity of surface water. The aim of the present study was to understand the influence of specific steps on toxicity and genotoxic...
Source: Environmental and Molecular Mutagenesis - October 19, 2009 Category: Molecular Biology Authors: Shao-Hua Xie, Ai-Lin Liu, Yan-Yan Chen, Li Zhang, Hui-Juan Zhang, Bang-Xiong Jin, Wen-Hong Lu, Xiao-Yan Li, Wen-Qing Lu Source Type: journals

Formaldehyde and leukemia: Epidemiology, potential mechanisms, and implications for risk assessmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Formaldehyde is widely used in the United States and other countries. Occupational and environmental exposures to formaldehyde may be associated with an increased risk of leukemia in exposed individuals. However, risk assessment of formaldehyde and leukemia has been challenging due to inconsistencies in human and animal studies and the lack of a known mechanism for leukemia induction. Here, we provide a summary of the symposium at the Environmental Mutagen Society Meeting in 2008, which focused on the epidemiology of formaldehyde and leukemia, potential mechanisms, and implication for risk assessment, with emphasis on futu...
Source: Environmental and Molecular Mutagenesis - September 29, 2009 Category: Molecular Biology Authors: Luoping Zhang, Laura E. Beane Freeman, Jun Nakamura, Stephen S. Hecht, John J. Vandenberg, Martyn T. Smith, Babasaheb R. Sonawane Source Type: journals

Flow cytometric scoring of micronucleated reticulocytes as a possible high-throughput radiation biodosimeterEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Micronucleated reticulocyte (MN-RET) scoring by flow cytometry (FCM) has been used in assessment of the clastogenic effects of chemicals. However, its dose-response to acute whole body irradiation (WBI) at moderate dose rates remains to be established. We show that FCM scoring of MN-RET in peripheral blood from male ICR mice exposed to WBI X-ray doses of 0.5-5 Gy at a dose rate of 0.488 Gy/min exhibits a linear dose-response relationship 24, 48, and 72 hr following WBI. Parallel microscopic counting of micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow smears from the same animals showed similar linear dose-...
Source: Environmental and Molecular Mutagenesis - September 28, 2009 Category: Molecular Biology Authors: Libo Liu, Yuguang Liu, Guangying Ni, Shuzheng Liu Source Type: journals

Cytogenetic genotoxicity of amoxicillinEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, AMO did not induce SCEs or CAs in human peripheral blood lymphocytes both in the presence and absence of the metabolic activator. AMO concentration-dependently decreased the proliferation index (PI) in the absence of the metabolic activation for 24-hr treatment period. Mitotic index (MI) was generally found to have been reduced when compared with the negative control but not with the solvent control in cultures treated with AMO for 24 hr. AMO did not decrease the PI and MI in the presence of the metabolic activator. Furthermore, AMO neither induced the formation of MN nor decreased the nuclear division index...
Source: Environmental and Molecular Mutagenesis - September 28, 2009 Category: Molecular Biology Authors: Erman Salih [Idot]stifli, Mehmet Topakta[scedil] Source Type: journals

Centrosome structure and function under normal and pathological conditionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No abstract. (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - September 22, 2009 Category: Molecular Biology Authors: Dan L. Sackett, Ofelia Olivero Source Type: journals

Induction of aneuploidy by single-walled carbon nanotubesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Engineered carbon nanotubes are newly emerging manufactured particles with potential applications in electronics, computers, aerospace, and medicine. The low density and small size of these biologically persistent particles makes respiratory exposures to workers likely during the production or use of commercial products. The narrow diameter and great length of single-walled carbon nanotubes (SWCNT) suggest the potential to interact with critical biological structures. To examine the potential of nanotubes to induce genetic damage in normal lung cells, cultured primary and immortalized human airway epithelial cells were exp...
Source: Environmental and Molecular Mutagenesis - September 21, 2009 Category: Molecular Biology Authors: L.M. Sargent, A.A. Shvedova, A.F. Hubbs, J.L. Salisbury, S.A. Benkovic, M.L. Kashon, D.T. Lowry, A.R. Murray, E.R. Kisin, S. Friend, K.T. McKinstry, L. Battelli, S.H. Reynolds Source Type: journals

Aurora A, centrosome structure, and the centrosome cycleEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The centrosome, also known as the microtubule organizing center of the cell, is a membrane-less organelle composed of a pair of barrel-shaped centrioles surrounded by electron-dense pericentriolar material. The centrosome progresses through the centrosome cycle in step with the cell cycle such that centrosomes are duplicated in time to serve as the spindle poles during mitosis and that each resultant daughter cell contains a single centrosome. Regulation of the centrosome cycle with relation to the cell cycle is an essential process to maintain the ratio of one centrosome per new daughter cell. Numerous mitosis-specific ki...
Source: Environmental and Molecular Mutagenesis - September 21, 2009 Category: Molecular Biology Authors: Kara B. Lukasiewicz, Wilma L. Lingle Source Type: journals

Nucleation capacity and presence of centrioles define a distinct category of centrosome abnormalities that induces multipolar mitoses in cancer cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Analysis of centrosome number and structure has become one means of assessing the potential for aberrant chromosome segregation and aneuploidy in tumor cells. Centrosome amplification directly causes multipolar catastrophic mitoses in mouse embryonic fibroblasts (MEFs) deficient for the tumor suppressor genes Brca1 or Trp53. We observed supernumerary centrosomes in cell lines established from aneuploid, but not from diploid, colorectal carcinomas; however, multipolar mitoses were never observed. This discrepancy prompted us to thoroughly characterize the centrosome abnormalities in these and other cancer cell lines with re...
Source: Environmental and Molecular Mutagenesis - September 20, 2009 Category: Molecular Biology Authors: Michael J. Difilippantonio, B. Michael Ghadimi, Tamara Howard, Jordi Camps, Quang Tri Nguyen, Douglas K. Ferris, Dan L. Sackett, Thomas Ried Source Type: journals

Human cell toxicogenomic analysis of bromoacetic acid: A regulated drinking water disinfection by-productEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this research was to integrate in vitro toxicology with focused toxicogenomic analysis of the regulated DBP, bromoacetic acid (BAA) and to evaluate modulation of gene expression involved in DNA damage/repair and toxic responses, with nontransformed human cells. We generated transcriptome profiles for 168 genes with 30 min and 4 hr exposure times that did not induce acute cytotoxicity. Using qRT-PCR gene arrays, the levels of 25 transcripts were modulated to a statistically significant degree in response to a 30 min treatment with BAA (16 transcripts upregulated and nine downregulated). The largest changes ...
Source: Environmental and Molecular Mutagenesis - September 14, 2009 Category: Molecular Biology Authors: Mark G. Muellner, Matias S. Attene-Ramos, Matthew E. Hudson, Elizabeth D. Wagner, Michael J. Plewa Source Type: journals

Centrosomes and myeloma; Aneuploidy and proliferationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple myeloma is the second most common hematological malignancy in the United States. The disease is characterized by an accumulation of clonal plasma cells. Clinically, patients present with anemia, lytic bone lesions, hypercalcaemia, or renal impairment. The genome of the malignant plasma cells is extremely unstable and is typically aneuploid and characterized by a complex combination of structure and numerical abnormalities. The basis of the genomic instability underlying myeloma is unclear. In this regard, centrosome amplification is present in about a third of myeloma and may represent a mechanism leading to genom...
Source: Environmental and Molecular Mutagenesis - September 8, 2009 Category: Molecular Biology Authors: Wee J. Chng, Rafael Fonseca Source Type: journals

Homage to Theodor Boveri (1862-1915): Boveri's theory of cancer as a disease of the chromosomes, and the landscape of genomic imbalances in human carcinomasEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No abstract. (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - September 7, 2009 Category: Molecular Biology Authors: Thomas Ried Source Type: journals

Synergistic genotoxicity caused by low concentration of titanium dioxide nanoparticles and p,p[prime]-DDT in human hepatocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The use of titanium dioxide nanoparticles (nano-TiO2) for the degradation of dichlorodiphenyltrichloroethane (p,p[prime]-DDT) increases the risk of exposure to trace nano-TiO2 and p,p[prime]-DDT mixtures. The interaction of p,p[prime]-DDT and nano-TiO2 at low concentrations may alter toxic response relative to nano-TiO2 or p,p[prime]-DDT alone. In this work, the combined genotoxicity of trace nano-TiO2 and p,p[prime]-DDT on human embryo L-02 hepatocytes without photoactivation was studied. Nano-TiO2 (0.1 g/L) was mixed with 0.01-1 mmol/L p,p[prime]-DDT to determine adsorption isotherms. L-02 cells were exposed to different...
Source: Environmental and Molecular Mutagenesis - August 25, 2009 Category: Molecular Biology Authors: Yun Shi, Jiang-Hua Zhang, Ming Jiang, Li-Hua Zhu, He-Qing Tan, Bin Lu Source Type: journals

Mutagenicity of blue rayon extracts of fish bile as a biomarker in a field studyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Blue rayon (BR) in combination with the Salmonella/microsome assay was used to evaluate the mutagenicity of fish bile samples. Specimens of Mugil curema from two sites were collected over a 1-year period. Piaçaguera channel contains high concentrations of total polycyclic aromatic hydrocarbons (PAHs) and other contaminants, while Bertioga channel was considered the reference sites in this study. Bile was extracted with BR and tested with TA98, TA100, and YG1041 strains with and without S9 in dose response experiments. PAH metabolite equivalents were analyzed using reverse-phase high performance liquid chromatography /fluo...
Source: Environmental and Molecular Mutagenesis - August 24, 2009 Category: Molecular Biology Authors: Patrícia Estevam dos Santos, Fábio Kummrow, Ana Cecília Rizzatti de Albergaria-Barbosa, Márcia Caruso Bícego, Gisela de Aragão Umbuzeiro Source Type: journals

An evaluation of the mode of action framework for mutagenic carcinogens case study II: Chromium (VI)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In response to the 2005 revised U.S Environmental Protection Agency's (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with additional information to determine whether the initiating step in carcinogenesis is through a mutagenic mode of action (MOA). This information is necessary to decide if age-dependent adjustment factors (ADAFs) should be applied to the risk assessment. Chromium (VI) [Cr (VI)], a carcinogen in animals and humans via inhalation, was reassessed by the National Toxicology Program (NTP) in 2-year drinking water studies in rodents. From these dat...
Source: Environmental and Molecular Mutagenesis - August 24, 2009 Category: Molecular Biology Authors: Nancy McCarroll, Nagalakshmi Keshava, Jonathan Chen, Gregory Akerman, Andrew Kligerman, Esther Rinde Source Type: journals

Micronucleus assay for mouse alveolar Type II and Clara cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of our study was to develop a micronucleus (MN) assay for detecting genotoxic damage after inhalation exposure in mouse alveolar Type II and Clara cells, potential target cells for lung carcinogens. Ten male C57BL/6J mice were exposed to ethylene oxide (630 mg/m3) for 4 hr via inhalation; 10 unexposed mice serving as controls. 72 hr after the exposure, Clara cells and alveolar Type II cells were isolated using two different methods. Method 1 included a 15-min trypsin lavage and a 2-hr incubation of cell suspension. Method 2 involved a 30-min trypsin lavage, Percoll gradient centrifugation, and a 48-hr incubat...
Source: Environmental and Molecular Mutagenesis - August 24, 2009 Category: Molecular Biology Authors: Hanna K. Lindberg, Ghita C.-M. Falck, Julia Catalán, Tiina Santonen, Hannu Norppa Source Type: journals

The human lung cell line A549 does not develop adaptive protection against the DNA-damaging action of formaldehydeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The alkaline comet assay was used to further characterize the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in the human lung cell line A549. DPX were indirectly measured as the reduction of gamma ray-induced DNA migration. Repeated treatments of A549 cells with low FA concentrations (up to 100 [mu]M) did not lead to significant differences in the induction of DPX in comparison with a single treatment. Pretreatment with higher FA-concentrations (200 [mu]M and above) enhanced the crosslinking effect. There was no indication for an adaptive protection against the induction of DPX by FA. The...
Source: Environmental and Molecular Mutagenesis - August 20, 2009 Category: Molecular Biology Authors: Günter Speit, Simone Neuss, Oliver Schmid Source Type: journals

Environmental Mutagen Society 40th Annual Meeting AbstractsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No abstract. (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - August 10, 2009 Category: Molecular Biology Source Type: journals

Flow cytometric detection of Pig-A mutant red blood cells using an erythroid-specific antibody: Application of the method for evaluating the in vivo genotoxicity of methylphenidate in adolescent ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A modified flow cytometry assay for Pig-A mutant rat red blood cells (RBCs) was developed using an antibody that positively identifies rat RBCs (monoclonal antibody HIS49). The assay was used in conjunction with a flow cytometric micronucleus (MN) assay to evaluate gene mutation and clastogenicity/aneugenicity in adolescent male and female rats treated with methylphenidate hydrochloride (MPH). Sprague-Dawley rats were treated orally with 3 mg/kg MPH (70/sex) or water (40/sex) 3 × /day on postnatal days (PNDs) 29-50. Eight additional rats (4/sex) were injected i.p. with N-ethyl-N-nitrosourea (ENU) on PND 28. Blood was coll...
Source: Environmental and Molecular Mutagenesis - August 5, 2009 Category: Molecular Biology Authors: Vasily N. Dobrovolsky, Sherin Y. Boctor, Nathan C. Twaddle, Daniel R. Doerge, Michelle E. Bishop, Mugimane G. Manjanatha, Takafumi Kimoto, Daishiro Miura, Robert H. Heflich, Sherry A. Ferguson Source Type: journals

K-Ras mutant fraction in A/J mouse lung increases as a function of benzo[a]pyrene doseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
K-Ras mutant fraction (MF) was measured to examine the default assumption of low-dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of 10 male A/J mice (7- to 9-weeks old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P and were sacrificed 28 days after treatment. K-Ras codon 12 TGT and GAT MFs in lung DNAs were measured using Allele-specific Competitive Blocker-PCR (ACB-PCR). The K-Ras codon 12 TGT geometric mean MF was 3.88 × 10-4 in controls, indicating an average of 1 mutation in every [sim]1,288 lung cells. The K-Ras codon 12 TGT geometric mean MFs were as follows: 3.56 ×...
Source: Environmental and Molecular Mutagenesis - August 4, 2009 Category: Molecular Biology Authors: Fanxue Meng, Geremy W. Knapp, Terry Green, Jeffrey A. Ross, Barbara L. Parsons Source Type: journals

Differential mutagenicity of aflatoxin B1 in the liver of neonatal and adult miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we have evaluated the effect of age on the mutagenicity of the fungal toxin and liver carcinogen aflatoxin B1 (AFB1). Neonatal Big Blue transgenic mice were treated with 6 mg/kg AFB1, a treatment that produces liver tumors, while adult mice were treated with 6 and 60 mg/kg AFB1, treatments that do not result in tumors. The cII liver mutant frequency (MF) in mice treated with AFB1 as neonates was 22-fold higher than in control neonatal mice, whereas the treatment of adult mice with either dose of AFB1 did not significantly increase the liver MF over the controls. In AFB1-treated neonatal mice, the frequency o...
Source: Environmental and Molecular Mutagenesis - July 29, 2009 Category: Molecular Biology Authors: Tao Chen, Robert H. Heflich, Martha M. Moore, Nan Mei Source Type: journals

DNA adduct kinetics in reproductive tissues of DNA repair proficient and deficient male mice after oral exposure to benzo(a)pyreneEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Benzo(a)pyrene (B[a]P) can induce somatic mutations, whereas its potential to induce germ cell mutations is unclear. There is circumstantial evidence that paternal exposure to B[a]P can result in germ cell mutations. Since DNA adducts are thought to be a prerequisite for B[a]P induced mutations, we studied DNA adduct kinetics by 32P-postlabeling in sperm, testes and lung tissues of male mice after a single exposure to B[a]P (13 mg/kg bw, by gavage). To investigate DNA adduct formation at different stages of spermatogenesis, mice were sacrificed at Day 1, 4, 7, 10, 14, 21, 32, and 42 after exposure. In addition, DNA repair ...
Source: Environmental and Molecular Mutagenesis - July 24, 2009 Category: Molecular Biology Authors: Nicole Verhofstad, Conny Th. M. van Oostrom, Jan van Benthem, Frederik J. van Schooten, Harry van Steeg, Roger W. L. Godschalk Source Type: journals

No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 daysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. []: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection wit...
Source: Environmental and Molecular Mutagenesis - July 23, 2009 Category: Molecular Biology Authors: Kristine L. Witt, David E. Malarkey, Cheryl A. Hobbs, Jeffrey P. Davis, Grace E. Kissling, William Caspary, Gregory Travlos, Leslie Recio Source Type: journals

Expression of caspase and apoptotic signal pathway induced by sulfur dioxideEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sulfur dioxide (SO2) is a common air pollutant that is released in low concentrations into the atmosphere and in higher concentrations in some work places. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00 ± 1.01, 28.00 ± 1.77, and 56.00 ± 3.44 mg/m3 SO2 for 7 days (6 hr/day), while control rats were exposed to filtered air under the same conditions. The mRNA and protein levels of caspase-3, caspase-8, and caspase-9 were analyzed using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and an immunohistochemistry method. Activities of caspase...
Source: Environmental and Molecular Mutagenesis - July 20, 2009 Category: Molecular Biology Authors: Juli Bai, Ziqiang Meng Source Type: journals

Mutagen structure and transcriptional response: Induction of distinct transcriptional profiles in Salmonella TA100 by the drinking-water mutagen MX and its homologuesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The relationship between chemical structure and biological activity has been examined for various compounds and endpoints for decades. To explore this question relative to global gene expression, we performed microarray analysis of Salmonella TA100 after treatment under conditions of mutagenesis by the drinking-water mutagen MX and two of its structural homologues, BA-1, and BA-4. Approximately 50% of the genes expressed differentially following MX treatment were unique to MX; the corresponding percentages for BA-1 and BA-4 were 91 and 80, respectively. Among these mutagens, there was no overlap of altered Kyoto Encycloped...
Source: Environmental and Molecular Mutagenesis - July 13, 2009 Category: Molecular Biology Authors: William O. Ward, Carol D. Swartz, Nancy M. Hanley, John W. Whitaker, Robert Franzén, David M. DeMarini Source Type: journals

Maintenance of bivalve hemocytes for the purpose of delayed DNA strand break assessment using the comet assayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The lack of appropriate methods for storing intact and viable cells for the purpose of delayed DNA strand break analysis has hitherto limited the application of the Comet assay to in vitro or in vivo laboratory studies and restricted ecologically more relevant field-collected samples to sites in proximity to suitable laboratory facilities. In the present article, osmotically corrected cell culture media Hanks Balanced Salt Solution (HBSS) and Leibovitz Media (L-15) were assessed for their suitability as temporary storage media of blue mussel (Mytilus edulis) hemocytes. It was found that hemocytes maintained in either HBSS ...
Source: Environmental and Molecular Mutagenesis - July 10, 2009 Category: Molecular Biology Authors: Mark G.J. Hartl, Steve J.W. Grigson, Emilie Sinet Source Type: journals

Centrosome abnormalities during porcine oocyte agingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study reports the dynamic changes of centrosomes and the microtubule cytoskeleton in porcine oocytes during aging and treatment by caffeine to restore spindle integrity in aging oocytes. We tested the effects of caffeine on the MII spindle with focus on microtubules and on the centrosome proteins [gamma]-tubulin and NuMA (nuclear mitotic apparatus protein). The results revealed that in porcine oocytes aged for 48 hr, centrosomes were absent and spindles became abnormal and disorganized; however, caffeine could prevent these changes or restore centrosome integrity in the meiotic spindle poles and displayed similar MII ...
Source: Environmental and Molecular Mutagenesis - July 9, 2009 Category: Molecular Biology Authors: Yi-liang Miao, Qing-Yuan Sun, Xia Zhang, Jian-Guo Zhao, Ming-Tao Zhao, Lee Spate, Randall S. Prather, Heide Schatten Source Type: journals

Role of the CYP2D6, EPHX1, MPO, and NQO1 genes in the susceptibility to acute lymphoblastic leukemia in Brazilian childrenEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of the present study was to evaluate the effect of the polymorphisms of debrisoquine hydroxylase (CYP2D6), epoxide hydrolase (EPHX1), myeloperoxidase (MPO), and quinone-oxoreductase (NQO1), which have been implicated in xenobiotic metabolism, on the risk of childhood acute lymphoblastic leukemia (ALL). We evaluated the frequency of polymorphisms in the CYP2D6 (*3 and *4), EPHX1 (*2 and *3), MPO (*2), and NQO1 (*2) genes in 206 patients with childhood ALL and in 364 healthy individuals matched for age and gender from a Brazilian population separated by ethnicity (European ancestry and African ancestry), using ...
Source: Environmental and Molecular Mutagenesis - July 9, 2009 Category: Molecular Biology Authors: Vanessa da Silva Silveira, Renata Canalle, Carlos Alberto Scrideli, Rosane Gomes de Paula Queiroz, Luiz Gonzaga Tone Source Type: journals

Neutrophil oxidative metabolism in Down syndrome patients with congenital heart defectsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Down syndrome (DS) occurs when an individual has three, rather than two, copies of the 21st chromosome. Cytosolic superoxide dismutase (SOD-1) is encoded by a gene on chromosome 21 and thus, SOD-1 activity is elevated in patients with DS. Forty percent of all cases with DS are associated with congenital heart defects (CHD). Although the contribution of SOD1 to disease phenotype is unknown, it is considered to be a "molecular marker" of the disease. It was hypothesized herein that the presence of CHD may alter the expression of SOD1 and oxidative metabolism in patients with DS. This hypothesis was tested via four experiment...
Source: Environmental and Molecular Mutagenesis - July 9, 2009 Category: Molecular Biology Authors: Ozlem Akinci, Ercan Mihci, Sukran Tacoy, Firat Kardelen, Ibrahim Keser, Mutay Aslan Source Type: journals

Hypothesis: Bifunctional mitochondrial proteins have centrosomal functionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria are dynamic organelles that are involved in a number of diverse processes. Most often the mitochondrion is associated with energy generation, but other important processes occur in this organelle such as fatty acid synthesis and amino acid metabolism. Although mitochondria encode less than 40 genes, all of the other [sim]1,000 genes required for their function are nuclear encoded. The protein products from these nuclear encoded genes are subsequently translocated to the mitochondria and utilized in the variety of processes within the organelle. Is it possible then that any of these nuclear encoded proteins cou...
Source: Environmental and Molecular Mutagenesis - June 29, 2009 Category: Molecular Biology Authors: Akilah Moore, Andy Golden Source Type: journals

Centrosome amplification induced by the antiretroviral nucleoside reverse transcriptase inhibitors lamivudine, stavudine, and didanosineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In cultured cells, exposure to the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine (AZT) induces genomic instability, cell cycle arrest, micronuclei, sister chromatid exchanges, and shortened telomeres. In previous studies, we demonstrated AZT-induced centrosome amplification (>2 centrosomes/cell). Here, we investigate centrosome amplification in cells exposed to other commonly used NRTIs. Experiments were performed using Chinese Hamster ovary (CHO) cells, and two normal human mammary epithelial cell (NHMEC) strains: M99005 and M98040, which are high and low incorporators of AZT into DNA, respectively. Cells w...
Source: Environmental and Molecular Mutagenesis - June 26, 2009 Category: Molecular Biology Authors: Mia Yu, Yvona Ward, Miriam C. Poirier, Ofelia A. Olivero Source Type: journals

Concordance analysis of an in vitro micronucleus screening assay and the regulatory chromosome aberration assay using pharmaceutical drug candidatesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The in vitro micronucleus assay is under consideration by regulatory agencies as a suitable alternative to the in vitro chromosome aberration (CA) assay. At Pfizer, we utilized a non-Good Laboratory practices cytokinesis-block in vitro micronucleus (CBMN) assay in CHO cells as a screen to predict the regulatory outcome of the human lymphocyte CA assay, and we have retrospectively analyzed a highly select set of 112 internal drug candidates to measure concordance. Overall, our exploratory CBMN correctly classified 97 of 112 (86.6%) compounds in the CA assay. Specificity was high with 87 of 92 (94.6%) CA negative compounds c...
Source: Environmental and Molecular Mutagenesis - June 24, 2009 Category: Molecular Biology Authors: Michael L. Homiski, Paula A. Muehlbauer, Krista L. Dobo, Maik J. Schuler, Jiri Aubrecht Source Type: journals

Analysis of genomic dose-response information on arsenic to inform key events in a mode of action for carcinogenicityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A comprehensive literature search was conducted to identify information on gene expression changes following exposures to inorganic arsenic compounds. This information was organized by compound, exposure, dose/concentration, species, tissue, and cell type. A concentration-related hierarchy of responses was observed, beginning with changes in gene/protein expression associated with adaptive responses (e.g., preinflammatory responses, delay of apoptosis). Between 0.1 and 10 [mu]M, additional gene/protein expression changes related to oxidative stress, proteotoxicity, inflammation, and proliferative signaling occur along with...
Source: Environmental and Molecular Mutagenesis - June 22, 2009 Category: Molecular Biology Authors: P. Robinan Gentry, Tracy B. McDonald, Dexter E. Sullivan, Annette M. Shipp, Janice W. Yager, Harvey J. Clewell III Source Type: journals

Comparison of the Salmonella/microsome microsuspension assay with the new microplate fluctuation protocol for testing the mutagenicity of environmental samplesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to compare the responses of the Salmonella/microsome microsuspension assay with the new microplate fluctuation protocol (MPF) for the evaluation of the mutagenic activity of environmental samples. Organic extracts of total particulate atmospheric air samples, surface waters, and effluents were tested in dose-response experiments. The assays were performed with strain TA98 in the absence and presence of S9 mix. Both protocols produced similar results, despite the fact that the maximum score of the MPF is limited to 48 wells, whereas in the regular plate assay it is possible to count up to 1,5...
Source: Environmental and Molecular Mutagenesis - May 31, 2009 Category: Molecular Biology Authors: Gisela de Aragão Umbuzeiro, Célia Maria Rech, Simone Correia, Ana Marcela Bergamasco, Giselli Helena Lima Cardenette, Sini Flückiger-Isler, Markus Kamber Source Type: journals

Human cytochrome P450 2E1 and sulfotransferase 1A1 coexpressed in Chinese hamster V79 cells enhance spontaneous mutagenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetic engineering of target cells for investigating the genotoxicity associated with specific xenobiotic-metabolizing enzymes is useful for elucidating metabolic activation and inactivation processes. We constructed a V79-derived cell line expressing both human cytochrome P450 (CYP) 2E1 and human sulfotransferase (SULT) 1A1. We previously reported that this cell line (V79-hCYP2E1-hSULT1A1) efficiently activates various important pro-genotoxicants. Here we present data on the expression level and stability of the heterologous enzymes, measured by immunoblotting, enzyme activities, and mutagenic responses to CYP2E1- and SU...
Source: Environmental and Molecular Mutagenesis - May 29, 2009 Category: Molecular Biology Authors: Yungang Liu, Hansruedi Glatt Source Type: journals

Effect of O6-alkylguanine-DNA alkyltransferase on genotoxicity of epihalohydrinsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The effect of O6-alkylguanine-DNA alkyltransferase (AGT) on the toxicity and mutagenicity of epihalohydrins was studied. AGT is a DNA repair protein that protects cells from agents that produce genotoxic O6-alkylguanine lesions by transferring the alkyl group to an internal cysteine residue (Cys145 in human AGT) in a single-step. This cysteine acceptor site is highly reactive and epihalohydrins reacted readily with AGT at this site with a halide order of reactivity of Br > Cl > F. AGT expression in bacterial cells caused a very large increase in the mutagenicity and cytotoxicity of epibromohydrin. The mutations were almost...
Source: Environmental and Molecular Mutagenesis - May 28, 2009 Category: Molecular Biology Authors: Aley G. Kalapila, Natalia A. Loktionova, Anthony E. Pegg Source Type: journals

Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrowEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Arsenic is a human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the skin and urinary bladder. Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include oxidative stress induction and inhibition of DNA damage repair. We investigated the effects of arsenic in drinking water on DNA damage repair in urinary bladder transitional cells and on micronucleus formation in bone marrow. F344 rats were given 100 ppm arsenate [As(V)] or dimethylarsinic acid [DMA(V)] in drinking water for 1 week. The in vivo repair of cyclophosphamide (CP)-induced DNA damage resulting from a single oral g...
Source: Environmental and Molecular Mutagenesis - May 26, 2009 Category: Molecular Biology Authors: Amy Wang, Andrew D. Kligerman, Steven D. Holladay, Douglas C. Wolf, John L. Robertson Source Type: journals

Suppression of the mouse double minute 4 gene causes changes in cell cycle control in a human mesothelial cell line responsive to ultraviolet radiation exposureEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The TP53 tumor suppressor gene is the most frequently inactivated gene in human cancer identified to date. However, TP53 mutations are rare in human mesotheliomas, as well as in many other types of cancer, suggesting that aberrant TP53 function may be due to alterations in its regulatory pathways. Mouse double minute 4 (MDM4) has been shown to be a key regulator of TP53 activity, both independently as well as in concert with its structural homolog, Mouse Double Minute 2 (MDM2). The purpose of this study was to characterize the effects of MDM4 suppression on TP53 and other proteins involved in cell cycle control before and ...
Source: Environmental and Molecular Mutagenesis - May 26, 2009 Category: Molecular Biology Authors: Melisa Bunderson-Schelvan, Amy K. Erbe, Corbin Schwanke, Mark A. Pershouse Source Type: journals

Radioprotective effects of Daflon against genotoxicity induced by gamma irradiation in human cultured lymphocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ability of Daflon to protect against genotoxicity induced by gamma irradiation has been investigated in vivo and in vitro in cultured lymphocytes from healthy human volunteers. Peripheral human blood samples were collected predose (10 min before) and 1, 2, and 3 hr after a single oral ingestion of 1000 mg of Daflon. At each time point, whole blood was exposed in vitro to 150 cGy of cobalt-60 gamma rays, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. For each volunteer, the results showed a significant increase in the incidence of ...
Source: Environmental and Molecular Mutagenesis - May 26, 2009 Category: Molecular Biology Authors: Seyed Jalal Hosseinimehr, Amirhossein Ahmadi, Aziz Mahmoudzadeh, Soheila Mohamadifar Source Type: journals

Folate deficiency in human peripheral blood lymphocytes induces chromosome 8 aneuploidy but this effect is not modified by riboflavinEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chromosome 8 aneuploidy is a common event in certain cancers but whether folate (F) deficiency induces chromosome 8 aneuploidy is not known. Furthermore the impact of riboflavin (R) deficiency, which may alter activity of a key enzyme in folate metabolism, on these events is unknown. Therefore, the aim of our research was to test the following hypotheses: (a) F deficiency induces chromosome 8 aneuploidy; (b) chromosome 8 aneuploidy is affected by F deficiency to a similar degree as chromosome 17 and (c) R deficiency aggravates the risk of aneuploidy caused by F deficiency. These hypotheses were tested in long-term cultures...
Source: Environmental and Molecular Mutagenesis - May 26, 2009 Category: Molecular Biology Authors: Juan Ni, Lin Lu, Michael Fenech, Xu Wang Source Type: journals

Evaluation of a suitable DNA damage biomarker for human biomonitoring of exposed workersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to identify a sensitive and noninvasive biomarker of early genotoxic effects, for health risk assessment of workers exposed to mixtures of low doses of xenobiotics. We studied 30 workers exposed to antineoplastic drugs, 57 workers exposed to different mixtures of polycyclic aromatic hydrocarbons (PAHs) (41 airport workers and 16 paving workers) and 76 controls. Comet and micronucleus (MN) tests were performed on lymphocytes and exfoliated buccal cells. The MN assay on lymphocytes did not show significant differences between exposed and controls, while the MN assay on exfoliated buccal cells ...
Source: Environmental and Molecular Mutagenesis - May 16, 2009 Category: Molecular Biology Authors: Delia Cavallo, Cinzia Lucia Ursini, Bruna Rondinone, Sergio Iavicoli Source Type: journals

Mutagenic potency of MMS-induced 1meA/3meC lesions in E. coliEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, special attention is focused on the mutagenic properties of 1meA/3meC which, by the activity of AlkB-dioxygenase, are quickly and efficiently converted to natural A/C bases in the DNA of E. coli alkB+ strains, preventing 1meA/3meC-induced mutations. We have found that in the absence of AlkB-mediated repair, MMS treatment results in an increased frequency of four types of base substitutions: GC[rarr]CG, GC[rarr]TA, AT[rarr]CG, and AT[rarr]TA, whereas overproduction of PolV in CC101-106 alkB-/pRW134 strains leads to a markedly elevated level of GC[rarr]TA, GC[rarr]CG, and AT[rarr]TA transversions. It has been...
Source: Environmental and Molecular Mutagenesis - May 15, 2009 Category: Molecular Biology Authors: Jadwiga Nieminuszczy, Damian Mielecki, Anna Sikora, Micha[lstrok] Wrzesi[nacute]ski, Aleksandra Chojnacka, Joanna Krwawicz, Celina Janion, El[zdot]bieta Grzesiuk Source Type: journals

The role of catechols and free radicals in benzene toxicity: An oxidative DNA damage pathwayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Benzene is a widespread volatile compound and an environmental contaminant. Since it causes important toxic effects in workers exposed to low levels, long-term exposure to this compound has been extensively studied. Leukemia, blood disorders, bone marrow depression, and some types of cancer are directly related to benzene-initiated toxicity. Bioactivation of benzene can lead to the formation of hazardous metabolites such as phenol, hydroquinone, and catechol. Catechol forms semiquinones and reactive quinones that are presumed to play an important role in the generation of reactive oxygen species (ROS). ROS formation can di...
Source: Environmental and Molecular Mutagenesis - May 15, 2009 Category: Molecular Biology Authors: George Barreto, Diego Madureira, Francisco Capani, Laura Aon-Bertolino, Ezequiel Saraceno, Lisandro Diego Alvarez-Giraldez Source Type: journals

The functional significance of centrosomes in mammalian meiosis, fertilization, development, nuclear transfer, and stem cell differentiationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Centrosomes had been discovered in germ cells and germ cells continue to provide excellent but also challenging material in which to study complex centrosomal dynamics. The present review highlights the importance of centrosomes for meiotic spindle integrity and the susceptibility of meiotic spindle centrosomes to aging and drugs or toxic agents which may be associated with female infertility, aneuploidy, and developmental abnormalities. We discuss cell and molecular aspects of centrosomes during fertilization, a critical stage in which centrosomes play crucial roles in precisely organizing the sperm aster that allows appo...
Source: Environmental and Molecular Mutagenesis - April 29, 2009 Category: Molecular Biology Authors: Heide Schatten, Qing-Yuan Sun Source Type: journals

The role of paraoxonase polymorphisms in the induction of micronucleus in paraoxon-treated human lymphocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme that has a role in the detoxification of organophosphorus compounds by hydrolyzing the bioactive oxons. PON1 polymorphims are responsible, at least in part, for the variation in the catalytic activity and expression of the enzyme and have been associated with susceptibility to organophosphorus pesticide toxicity, mainly neurotoxicity. The aim of this study was to determine whether paraoxon induced micronuclei and to examine the role of PON1 polymorphism in paraoxon's genotoxic potential. First, dose finding cytogenetic experiments were performed on ...
Source: Environmental and Molecular Mutagenesis - April 28, 2009 Category: Molecular Biology Authors: Aurora E. Rojas-García, Monserrat Sordo, Libia Vega, Bezabet Quintanilla-Vega, Maria Solis-Heredia, Patricia Ostrosky-Wegman Source Type: journals

Dependence of DNA double strand break repair pathways on cell cycle phase in human lymphoblastoid cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DNA double-strand breaks (DSBs) are usually repaired by nonhomologous end-joining (NHEJ) or homologous recombination (HR). NHEJ is thought to be the predominant pathway operating in mammalian cells functioning in all phases of the cell cycle, while HR works in the late-S and G2 phases. However, relative contribution, competition, and dependence on cell cycle phases are not fully understood. We previously developed a system to trace the fate of DSBs in the human genome by introducing the homing endonuclease I-SceI site into the thymidine kinase (TK) gene of human lymphoblastoid TK6 cells. Here, we use this system to investi...
Source: Environmental and Molecular Mutagenesis - April 28, 2009 Category: Molecular Biology Authors: Yoshio Takashima, Mayumi Sakuraba, Tomoko Koizumi, Hiroko Sakamoto, Makoto Hayashi, Masamitsu Honma Source Type: journals

Effect of annatto on micronuclei induction by direct and indirect mutagens in HepG2 cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we evaluated the ability of AN to protect human hepatoma cells (HepG2) from micronucleus (MN) induction against three different mutagens: benzo(a)pyrene (B(a)P), doxorubicin (DXR), and methyl methanesulfonate (MMS). In an attempt to clarify the possible mechanism of antimutagenicity of AN, three protocols of treatment were applied (pretreatment; simultaneous treatment, and post-treatment with AN following treatment with the mutagens). Also, cells exposed only to AN were assayed for cytotoxicity and mutagenicity. A dosage up to 10 [mu]g/ml of AN was devoid of mutagenic activity. Protective effects were seen o...
Source: Environmental and Molecular Mutagenesis - April 28, 2009 Category: Molecular Biology Authors: Gustavo Rafael Mazzaron Barcelos, José Pedro Friedmann Angeli, Juliana Mara Serpeloni, Bruno Alves Rocha, Mário Sérgio Mantovani, Lusânia Maria Greggi Antunes Source Type: journals

Evaluation of genome damage and its relation to oxidative stress induced by glyphosate in human lymphocytes in vitroEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the present study we evaluated the genotoxic and oxidative potential of glyphosate on human lymphocytes at concentrations likely to be encountered in residential and occupational exposure. Testing was done with and without metabolic activation (S9). Ferric-reducing ability of plasma (FRAP), thiobarbituric acid reactive substances (TBARS) and the hOGG1 modified comet assay were used to measure glyphosate's oxidative potential and its impact on DNA. Genotoxicity was evaluated by alkaline comet and analysis of micronuclei and other nuclear instabilities applying centromere probes. The alkaline comet assay showed significan...
Source: Environmental and Molecular Mutagenesis - April 28, 2009 Category: Molecular Biology Authors: Marin Mladinic, Suzana Berend, Ana Lucic Vrdoljak, Nevenka Kopjar, Bozica Radic, Davor Zeljezic Source Type: journals