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Environmental and Molecular Mutagenesis

Martin F Arlt, Sountharia Rajendran, Sandra N Holmes, Kathleen Wang, Ingrid L Bergin, Samreen Ahmed, Thomas E Wilson, Thomas W Glover
Copy number variants (CNVs) are important in genome variation and genetic disease, with new mutations arising frequently in the germline and somatic cells. Replication stress caused by aphidicolin and hydroxyurea (HU) is a potent inducer of de novo CNVs in cultured mammalian cells. HU is used extensively for long-term management of sickle cell disease. Here, we examined the effects of HU treatment on germline CNVs in vivo in male mice to explore whether replication stress can act as a CNV mutagen in germline mitotic divisions as in cultured cells and whether this would support a concern for increased CNV mutations in offspring of men treated with HU...
September 15, 2018: Environmental and Molecular Mutagenesis
Claire M Koenig, Carol Beevers, Kamala Pant, Robert R Young
Splenic tumors have been reported in rat cancer bioassays with para-chloroaniline (PCA) and aniline. Development of these tumors is hypothesized to be due to hematotoxicity via the formation of methemoglobin (MetHb) and not direct DNA reactivity. To evaluate the mode of action (MOA) for tumor formation a transgenic rodent (TGR) in vivo gene mutation assay in Big Blue® TgF344 rats was performed with parallel micronuclei analysis in peripheral blood. Male rats were gavaged daily for 28 d to 0.5, 15, and 60 mg/kg PCA and 100 mg/kg aniline, the base molecular structure of PCA...
September 14, 2018: Environmental and Molecular Mutagenesis
Xiang Wan, Yu Zhang, Mei Lan, Meng-Hao Pan, Feng Tang, Hao-Lin Zhang, Xiang-Hong Ou, Shao-Chen Sun
Kinesin superfamily proteins (KIFs) act as molecular motors and are involved in material transport along microtubules to maintain normal cellular functions. KIF11 (also named kinesin-5, Eg5, and KSP) is a plus-end-directed homotetrameric kinesin that regulates spindle formation for actuate chromosomal separation during mitosis. However, the roles of KIF11 in meiosis are still unclear. In this study, we investigated the regulatory functions of KIF11 during porcine oocyte maturation. The results indicated that KIF11 was expressed in different stages during porcine oocyte meiosis...
August 28, 2018: Environmental and Molecular Mutagenesis
Natalie Saini, Dmitry A Gordenin
Somatic genome instability is a hallmark of cancer genomes and has been linked to aging and a variety of other pathologies. Large-scale cancer genome and exome sequencing have revealed that mutation load and spectra in cancers can be influenced by environmental exposures, the anatomical site of exposures, and tissue type. There is now an abundance of data favoring the hypothesis that a substantial portion of the mutations in cancers originate prior to carcinogenesis in stem cells of the healthy individual. Rapid advances in sequencing of noncancer cells from healthy humans have shown that their mutation loads and spectra resemble cancer data...
August 27, 2018: Environmental and Molecular Mutagenesis
Fábio Henrique Fernandes, Mrio Otvio Botasso-Nasciutti, Andr Luiz Ventura Svio, Leonardo da Cunha Menezes Souza, Jhennifer Rebecca Fernandes-Cal, Fbio Florena Cardoso, Marcos Roberto de Mattos Fontes, Anjana Fernandes Albuquerque, Carla C Munari, Fbio Kummrow, Gisela de Aragão Umbuzeiro, Daisy Maria Fvero Salvadori
Color Index (C.I.) Disperse Red 1 (DR1) is a widely used textile azo dye found in rivers. As it may not be completely removed by conventional treatments, humans can be exposed through drinking water. Studies have supported in vitro toxicity and mutagenicity of commercial DR1. This study aimed to investigate the mutagenic and toxicogenomic effects of commercial DR1 in multiple tissues/organs of Swiss male mice. For that, animals were orally exposed to the dye (by gavage), at single doses of 0.0005, 0.005, 0...
August 27, 2018: Environmental and Molecular Mutagenesis
Javier R Revollo, Mason G Pearce, Azra Dad, Dayton M Petibone, Timothy W Robison, Daniel Roberts, Vasily N Dobrovolsky
We have established a flow cytometry-based Pig-a assay for rat bone marrow erythroid cells (BMEs). The BME Pig-a assay uses a DNA-specific stain and two antibodies: one against the transmembrane transferrin receptor (CD71 marker) and the other against the GPI-anchored complement inhibitory protein (CD59 marker). In F344 male rats treated acutely with a total of 120 mg/kg of N-ethyl-N-nitrosourea (ENU) the frequency of CD59-deficient phenotypically mutant BMEs increased approximately 24-fold compared to the rats concurrently treated with the vehicle...
August 9, 2018: Environmental and Molecular Mutagenesis
Azra Dad, Javier R Revollo, Dayton M Petibone, Mason G Pearce, Robert H Heflich, Vasily N Dobrovolsky
The in vivo erythrocyte Pig-a gene mutation assay measures the phenotypic loss of GPI-anchored surface markers. Molecular analysis of the marker-deficient erythrocytes cannot provide direct proof that the mutant phenotype is due to mutation in the Pig-a gene because mammalian erythrocytes lack genomic DNA. Granulocytes are nucleated cells that originate from myeloid progenitor cells in bone marrow as is the case for erythrocytes, and thus analysis of Pig-a mutation in bone marrow granulocytes can provide information about the source of mutations detected in the erythrocyte Pig-a assay...
August 9, 2018: Environmental and Molecular Mutagenesis
Dejun Huang, Xiaoning Zhang, Chen Zhang, Hui Li, Dong Li, Yan Hu, Feng Yang, Yongmei Qi
2,4-Dichlorophenol (2,4-DCP) is one of the most abundant chlorophenols in the aquatic environment and has been frequently detected in surface waters. Although ecological and cellular toxicity of 2,4-DCP has aroused the public concern, few reports focus on the genotoxicity, especially on DNA double strand breaks (DSBs), of 2,4-DCP in fish. The present study aims to explore the genotoxic effect of 2,4-DCP on DSBs in goldfish Carassius auratus and to further elucidate its potential mechanism. The results showed that 2,4-DCP significantly induced DSBs (detected by neutral comet assay) in erythrocytes and hepatocytes of goldfish in a dose-dependent manner, indicating a genotoxicity of 2,4-DCP on fish...
August 9, 2018: Environmental and Molecular Mutagenesis
Yann Guéguen, Nicholas D Priest, Isabelle Dublineau, Laura Bannister, Marc Benderitter, Christelle Durand, Teni G Ebrahimian, Eric Grégoire, Stéphane Grison, Chrystelle Ibanez, Audrey Legendre, Philippe Lestaevel, Sandrine Roch-Lefèvre, Laurence Roy, Karine Tack, Heather Wyatt, Julie Leblanc, Jean-René Jourdain, Dmitry Klokov
Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta-emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explores the gaps in this knowledge and provides recommendations on the best ways forward for improving our understanding of the health effects of low-level exposure to it...
August 2018: Environmental and Molecular Mutagenesis
Evagelia C Laiakis, Tytus D Mak, Steven J Strawn, Yi-Wen Wang, Bo-Hyun Moon, Pelagie Ake, Albert J Fornace
Exposures to ionizing radiation (IR) may either be accidental or intentional, for medical purposes or even through terrorist actions. As certain populations emerge to be more radiosensitive than others, it is imperative to assess those individuals and treat them accordingly. To demonstrate the feasibility of rapid identification of such cases, we utilized the highly radiosensitive mouse model Atm-/- in the C57BL/6 background, and evaluated the urinary responses in 8-10 week old male mice at early time points (4, 24, and 72 h) after exposure to their respective LD50/30 doses [4 Gy for Atm-/- , and 8 Gy for wild type (WT)]...
August 2018: Environmental and Molecular Mutagenesis
Zareen Sultana, Biswabandhu Bankura, Arup Kumar Pattanayak, Debmalya Sengupta, Mainak Sengupta, Makhan Lal Saha, Chinmay Kumar Panda, Madhusudan Das
Interleukin 1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL-1β and TNF-α genes were genotyped in 120 GC patients and 135 healthy individuals. Combined effect of the SNPs in both genes with GC risk was determined through allele dosage analysis (ADA) and the survival data were analyzed by Log Rank Test...
August 2018: Environmental and Molecular Mutagenesis
Caren Weinhouse, Lisa Truong, Joel N Meyer, Patrick Allard
The roundworm Caenorhabitis elegans has been an established model organism for the study of genetics and developmental biology, including studies of transcriptional regulation, since the 1970s. This model organism has continued to be used as a classical model system as the field of transcriptional regulation has expanded to include scientific advances in epigenetics and chromatin biology. In the last several decades, C. elegans has emerged as a powerful model for environmental toxicology, particularly for the study of chemical genotoxicity...
August 2018: Environmental and Molecular Mutagenesis
Hervé Perdry, Kristine B Gutzkow, Marianne Chevalier, Laurence Huc, Gunnar Brunborg, Elisa Boutet-Robinet
Even if the comet assay has been widely used for decades, there is still a need for controlled studies and good mathematical models to assess the variability of the different versions of this assay and in particular to assess potential intra-experimental variability of the high-throughput comet assay. To address this point, we further validate a high-throughput comet assay that uses hydrophilic polyester film (Gelbond®). Experiments were performed using human peripheral blood mononuclear cells (PBMC) either untreated or treated with different concentration of MMS (methyl methanesulfonate)...
August 2018: Environmental and Molecular Mutagenesis
Aqila A Ahmed, Cristine Smoczer, Brianna Pace, David Patterson, Diane Cress Cabelof
We aim to establish that accelerated aging and premature cellular senescence seen in individuals with Down syndrome is related to reduced DNA polymeraseβ. We report here that primary fibroblasts from Down syndrome individuals exhibit greater SA-β-gal staining (fourfold increase, P < 0.001), increased p16 transcript abundance (threefold increase, P < 0.01), and reduced HMGB1 nuclear localization (1.5-fold lower, P < 0.01). We also find that DNA polymerase β expression is significantly reduced in Down syndrome primary fibroblasts (53% decline, P < 0...
August 2018: Environmental and Molecular Mutagenesis
Karina Acevedo-Whitehouse, Kathy J Cole, David H Phillips, Paul D Jepson, Rob Deaville, Volker M Arlt
One level at which persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons PAHs) can exert damage is by causing DNA strand-breaks or nucleotide base modifications, which, if unrepaired, can lead to embryonic mutations, abnormal development and cancer. In marine ecosystems, genotoxicity is expected to be particularly strong in long-lived apex predators due to pollutant bioaccumulation. We conducted 32 P-postlabeling analyses optimized for the detection and quantification of aromatic/hydrophobic DNA adducts in the livers of 40 sexually-mature North Atlantic harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines...
August 2018: Environmental and Molecular Mutagenesis
Rocío López-Vargas, Alejandra Méndez-Serrano, Arnulfo Albores-Medina, Fernando Oropeza-Hernández, Leticia Hernández-Cadena, Franciso Mercado-Calderón, Esmeralda Alvarado-Toledo, Selene Herrera-Morales, Omar Arellano-Aguilar, Guadalupe García-Vargas, Regina Montero-Montoya
Although the Atoyac River has been classified as highly polluted by environmental authorities, several communities are settled on its banks, affecting around 1.5 million persons, as well as farmland, due to an environmental distribution of toxics in the area. Our aim was to demonstrate that this environment affects important physiological processes that have an impact in health, so we conducted a study of schoolchildren from small communities on the banks of the river and in another similar town located far from it...
August 2018: Environmental and Molecular Mutagenesis
Paula Hauber Gameiro, Naiara Costa Pereira, Jocelita Aparecida Vaz Rocha, Karen Alam Leal, Vera Maria Ferrão Vargas
Soil contamination enters aquatic ecosystems affecting sediment quality. The region studied is the Taquari River, Brazil, close to a site contaminated by wood preservatives, with a runoff route into the river. The first stage of the remediation process (In this article, the terms intervention and remediation have been used with slightly different meanings. We consider intervention to be the first phase of the remediation process, which aims to remove active sources) was an intervention to remove the main active sources...
August 2018: Environmental and Molecular Mutagenesis
Sami S Qutob, Vinita Chauhan, Byron Kuo, Andrew Williams, Carole L Yauk, James P McNamee, B Gollapudi
Considerable data has been generated to elucidate the transcriptional response of cells to ultraviolet radiation (UVR) exposure providing a mechanistic understanding of UVR-induced cellular responses. However, using these data to support standards development has been challenging. In this study, we apply benchmark dose (BMD) modeling of transcriptional data to derive thresholds of gene responsiveness following exposure to solar-simulated UVR. Human epidermal keratinocytes were exposed to three doses (10, 20, 150 kJ/m2 ) of solar simulated UVR and assessed for gene expression changes 6 and 24 hr postexposure...
July 2018: Environmental and Molecular Mutagenesis
Maria Helena Guerra Andersen, Anne Thoustrup Saber, Julie Elbaek Pedersen, Peter Bøgh Pedersen, Per Axel Clausen, Mille Løhr, Ali Kermanizadeh, Steffen Loft, Niels E Ebbehøj, Åse Marie Hansen, Ismo Kalevi Koponen, Eva-Carina Nørskov, Ulla Vogel, Peter Møller
Firefighting is regarded as possibly carcinogenic, although there are few mechanistic studies on genotoxicity in humans. We investigated exposure to polycyclic aromatic hydrocarbons (PAH), lung function, systemic inflammation and genotoxicity in peripheral blood mononuclear cells (PBMC) of 22 professional firefighters before and after a 24-h work shift. Exposure was assessed by measurements of particulate matter (PM), PAH levels on skin, urinary 1-hydroxypyrene (1-OHP) and self-reported participation in fire extinguishing activities...
July 2018: Environmental and Molecular Mutagenesis
Li-Bo Yu, Yu-Ting Tu, Jing-Wen Huang, Ya-Nan Zhang, Guo-Qiao Zheng, Xiao-Wen Xu, Jin-Wei Wang, Jean Qin Xiao, David C Christiani, Zhao-Lin Xia
Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead-exposed workers were divided into two groups according to their B-Pb P50 value, with other 50 lead-unexposed workers as a control group...
July 2018: Environmental and Molecular Mutagenesis
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