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Environmental and Molecular Mutagenesis

B Kopp, D Zalko, M Audebert
Heavy metals, such as arsenic (As), antimony (Sb), barium (Ba), cadmium (Cd), cobalt (Co), germanium (Ge), lead (Pb), nickel (Ni), tellurium (Te), and vanadium (V) are widely distributed in the environment and in the food chain. Human exposure to heavy metals through water and food has been reported by different international agencies. Although some of these heavy metals are essential elements for human growth and development, they may also be toxic at low concentrations due to indirect mechanisms. In this study, the genotoxic and cytotoxic properties of 15 different oxidation statuses of 11 different heavy metals were investigated using high-throughput screening (γH2AX assay) in two human cell lines (HepG2 and LS-174T) representative of target organs (liver and colon) for food contaminants...
November 18, 2017: Environmental and Molecular Mutagenesis
Helena Moratin, Agmal Scherzad, Thomas Gehrke, Pascal Ickrath, Katrin Radeloff, Norbert Kleinsasser, Stephan Hackenberg
The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells...
November 18, 2017: Environmental and Molecular Mutagenesis
Akin Çayir, Mahmut Coskun, Munevver Coskun, Hayal Cobanoglu
Pesticides widely used in agriculture and other applications have been linked to cancer and other diseases through several potential mechanisms. The goals of this study were to assess DNA damage in lymphocytes by the cytokinesis-block micronucleus assay (CBMN), and to measure circulating cell free DNA (ccf-DNA) in the blood of pesticide-exposed greenhouse workers and matched controls living in the same area. CBMN was applied to peripheral blood lymphocyte samples taken at different times (spring and autumn) for each individual...
November 11, 2017: Environmental and Molecular Mutagenesis
Rebecca Troisi, Elizabeth E Hatch, Linda Titus, William Strohsnitter, Mitchell H Gail, Dezheng Huo, Ervin Adam, Stanley J Robboy, Marianne Hyer, Robert N Hoover, Julie R Palmer
In the Diethylstilbestrol [DES] Combined Cohort Follow-up, the age- and calendar-year specific standardized incidence ratio [SIR] for clear cell adenocarcinoma [CCA] was 27.6 (95% confidence interval [CI] 7.51-70.6) for the exposed women. The SIR for breast cancer was 1.17 (95% CI 1.01-1.36) and the hazard ratio [HR] adjusted for birth year and cohort for comparison with the unexposed was 1.05 (95% CI 0.79-1.41). The SIR for pancreatic cancer was 2.43 (95% CI 1.21-4.34) and the adjusted HR for comparison with unexposed women was 7...
November 10, 2017: Environmental and Molecular Mutagenesis
Xiaoqing Guo, Robert H Heflich, Stacey L Dial, Mamata De, Patricia A Richter, Nan Mei
In vitro genotoxicity dose-response data have been investigated for their utility in modeling and assessing potential differences in mutagenic responses between machine-generated whole smoke solutions (WSSs) from combusted cigarette tobacco products. Our previous study observed that potency ranking by benchmark dose (BMD) analysis was a useful modeling approach for quantitative assessment of differences between the mutagenicity of several structurally diverse chemical constituents of cigarette smoke. To follow-up on these observations, we used the mouse lymphoma assay (MLA) to evaluate the mutagenicity of WSSs prepared from two commercial cigarettes smoked under two different smoking machine regimens...
November 9, 2017: Environmental and Molecular Mutagenesis
Jeffrey C Bemis, Svetlana L Avlasevich, Carson Labash, Page McKinzie, Javier Revollo, Vasily N Dobrovolsky, Stephen D Dertinger
Lack of cell surface glycosylphosphatidylinositol (GPI)-anchored protein(s) has been used as a reporter of Pig-a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the cell surface of the mouse lymphoma cell line L5178Y/Tk(+/-) . Cells were exposed to mutagenic and nonmutagenic compounds for 24 hr followed by washout and incubation for an additional 7 days. Following this mutant manifestation time, cells were labeled with fluorescent antibodies against CD90...
November 8, 2017: Environmental and Molecular Mutagenesis
Giovanni Fiorito, Jelle Vlaanderen, Silvia Polidoro, John Gulliver, Claudia Galassi, Andrea Ranzi, Vittorio Krogh, Sara Grioni, Claudia Agnoli, Carlotta Sacerdote, Salvatore Panico, Ming-Yi Tsai, Nicole Probst-Hensch, Gerard Hoek, Zdenko Herceg, Roel Vermeulen, Akram Ghantous, Paolo Vineis, Alessio Naccarati
Air pollution is associated with a broad range of adverse health effects, including mortality and morbidity due to cardio- and cerebrovascular diseases (CCVD), but the molecular mechanisms involved are not entirely understood. This study aims to investigate the involvement of oxidative stress and inflammation in the causal chain, and to identify intermediate biomarkers that are associated retrospectively with the exposure and prospectively with the disease. We designed a case-control study on CCVD nested in a cohort of 18,982 individuals from the EPIC-Italy study...
November 8, 2017: Environmental and Molecular Mutagenesis
Yiying Wang, Javier Revollo, Page McKinzie, Mason G Pearce, Azra Dad, Berran Yucesoy, Hans Rosenfeldt, Robert H Heflich, Vasily N Dobrovolsky
The X-linked Pig-a gene encodes an enzyme required for the biosynthesis of glycosyl phosphatidylinositol (GPI) anchors. Pig-a mutant cells fail to synthesize GPI and to express GPI-anchored protein markers (e.g., CD90) on their surface. Marker deficiency serves as a phenotypic indicator of Pig-a mutation in various in vivo assays. Here, we describe an in vitro Pig-a mutation assay in L5178YTk(+/-) mouse lymphoma cells, in which mutant-phenotype cells are measured by flow cytometry using a fluorescent anti-CD90 antibody...
November 2, 2017: Environmental and Molecular Mutagenesis
John Nicolette, Joel Murray, Paul Sonders, Bruce Leroy
The in vivo rodent Pig-a mutation assay is a sensitive test to identify exposure to mutagenic substances, and has been proposed as an assay for the identification of impurities for pharmaceuticals. Red blood cells (RBCs) and reticulocytes (RETs) are analyzed by flow cytometry after exposure to potentially mutagenic chemicals for cells deficient in the cell surface anchored protein CD59, representing mutation in the X-linked Pig-a gene. The full potential of the assay as well as its limitations are currently being explored...
October 27, 2017: Environmental and Molecular Mutagenesis
Debmalya Sengupta, Udayan Guha, Samsiddhi Bhattacharjee, Mainak Sengupta
Candidate gene as well as genome-wide association studies identified several polymorphic variants to be associated with lung cancer worldwide including in India. However, contradictory results have failed to estimate the overall effect of the polymorphic variants on the disease. Textmining was conducted on PubMed following specific search strings to gather all the publications related to genetic association with lung cancer in India. Out of 211 PubMed hits only 30 studies were selected for meta-analysis following specific inclusion criteria...
October 27, 2017: Environmental and Molecular Mutagenesis
Kenichi Masumura, Naomi Toyoda-Hokaiwado, Naoko Niimi, Petr Grúz, Naoko A Wada, Akira Takeiri, Kou-Ichi Jishage, Masayuki Mishima, Takehiko Nohmi
DNA polymerase kappa (Polk) is a specialized DNA polymerase involved in translesion DNA synthesis. To understand the protective roles against genotoxins in vivo, we established inactivated Polk knock-in gpt delta (inactivated Polk KI) mice that possessed reporter genes for mutations and expressed inactive Polk. In this study, we examined genotoxicity of benzo[a]pyrene (BP) to determine whether Polk actually suppressed BP-induced genotoxicity as predicted by biochemistry and in vitro cell culture studies. Seven-week-old inactivated Polk KI and wild-type (WT) mice were treated with BP at doses of 5, 15, or 50 mg/(kg·day) for three consecutive days by intragastric gavage, and mutations in the colon and micronucleus formation in the peripheral blood were examined...
October 27, 2017: Environmental and Molecular Mutagenesis
S M J Mortazavi
No abstract text is available yet for this article.
October 25, 2017: Environmental and Molecular Mutagenesis
Yuhui Zhang, Lei Xie, Xinyi Li, Lihong Chai, Mengxing Chen, Xiaojing Kong, Qingqing Wang, Jingfei Liu, Lijuan Zhi, Chang Yang, Hongyuan Wang
Excessive fluoride in natural water ecosystem has the potential to detrimentally affect amphibians, but little is known of such effects or underlying mechanisms in Bufo gargarizans embryos. In the present study, the effects of fluoride exposure on B. gargarizans embryos were investigated. First, fluoride teratogenic experiment showed that the 9 days EC50 of fluoride on B. gargarizans embryos was 177.62 mg/L. Then, we studied the sublethal effects of fluoride on B. gargarizans embryos at control, 0.7, 4.1, 19...
October 12, 2017: Environmental and Molecular Mutagenesis
Yufei Dai, Dianzhi Ren, Bryan A Bassig, Roel Vermeulen, Wei Hu, Yong Niu, Huawei Duan, Meng Ye, Tao Meng, Jun Xu, Ping Bin, Meili Shen, Jufang Yang, Wei Fu, Kees Meliefste, Debra Silverman, Nathaniel Rothman, Qing Lan, Yuxin Zheng
The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross-sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection...
October 12, 2017: Environmental and Molecular Mutagenesis
Clara Bocchi, Cristina Bazzini, Federica Fontana, Giancarlo Pinto, Francesca Cassoni
Airborne particulate matter (PM) has long been recognized as a potential health hazard and in 2013 was classified as carcinogenic to humans by the International Agency for Research on Cancer. In this study we evaluate and compare mutagenic and genotoxic potencies of PM2.5 collected in three seasons, from 2012 to 2015, in five Italian cities. Mutagenicity was evaluated through the Ames test on TA98 and TA100 strains and, for the measurement of PM clastogenicity, Comet assay was carried out on cultured human lung cells (A549)...
October 11, 2017: Environmental and Molecular Mutagenesis
Michael D Wyatt, Nicole M Reilly, Shikha Patel, Preeti Rajesh, Gary P Schools, Phillip G Smiraldo, Douglas L Pittman
Thiopurines are part of a clinical regimen used for the treatment of autoimmune disorders and childhood acute lymphoblastic leukemia. However, despite these successes, there are also unintended consequences such as therapy-induced cancer in long-term survivors. Therefore, a better understanding of cellular responses to thiopurines will lead to improved and personalized treatment strategies. RAD51D is an important component of homologous recombination (HR), and our previous work established that mammalian cells defective for RAD51D are more sensitive to the thiopurine 6-thioguanine (6TG) and have dramatically increased numbers of multinucleated cells and chromosome instability...
September 25, 2017: Environmental and Molecular Mutagenesis
John W Wills, George E Johnson, Hannah L Battaion, Wout Slob, Paul A White
There is growing interest in quantitative analysis of in vivo genetic toxicity dose-response data, and use of point-of-departure (PoD) metrics such as the benchmark dose (BMD) for human health risk assessment (HHRA). Currently, multiple transgenic rodent (TGR) assay variants, employing different rodent strains and reporter transgenes, are used for the assessment of chemically-induced genotoxic effects in vivo. However, regulatory issues arise when different PoD values (e.g., lower BMD confidence intervals or BMDLs) are obtained for the same compound across different TGR assay variants...
September 25, 2017: Environmental and Molecular Mutagenesis
Guang-Hui Zhang, Ye Lu, Bu-Qiang Ji, Jing-Chao Ren, Pin Sun, Shibin Ding, Xiaoling Liao, Kaiju Liao, Jinyi Liu, Jia Cao, Qing Lan, Nathaniel Rothman, Zhao-Lin Xia
Global DNA hypomethylation is commonly observed in benzene-exposed workers, but the underlying mechanisms remain unclear. We sought to discover the relationships among reduced white blood cell (WBC) counts, micronuclear (MN) frequency, and global DNA methylation to determine whether there were associations with mutations in DNMT3A/3B. Therefore, we recruited 410 shoe factory workers and 102 controls from Wenzhou in Zhenjiang Province. A Methylated DNA Quantification Kit was used to quantify global DNA methylation, and single nucleotide polymorphisms (SNPs) in DNMT3A (rs36012910, rs1550117, and R882) and DNMT3B (rs1569686, rs2424909, and rs2424913) were identified using the restriction fragment length polymorphism method...
September 25, 2017: Environmental and Molecular Mutagenesis
Rufeng Shi, Jiangbo Li, Jiyun He, Qingtao Meng, Zhiping Qian, Di Shi, Qi Liu, Yali Cai, Xinran Li, Xiaoping Chen
Tibetans have a higher essential hypertension prevalence compared with other ethnics in China. The reason might be due to their unique environmental influence, as well as genetic factor. However, limited studies focus on Tibetan genetics and its association with hypertension. The aim of this study was to investigate the association between With-No-Lysine (K) Kinase 1 (WNK1), Serine/Threonine kinase 39(STK39) genes variants and hypertension in the Tibetan population. 204 Tibetan hypertensive patients and 305 normotensive controls were recruited in an epidemiological survey conducted at 2 sites in the Ganzi Tibetan autonomous region...
September 25, 2017: Environmental and Molecular Mutagenesis
Sabrina Wilde, Miriam Dambowsky, Claudia Hempt, Andreas Sutter, Nina Queisser
Regulatory in vitro genotoxicity testing exhibits shortcomings in specificity and mode of action (MoA) information. Thus, the aim of this work was to evaluate the performance of the novel MultiFlow(®) assay composed of mechanistic biomarkers quantified in TK6 cells after treatment (4 and 24 hr): γH2AX (DNA double strand breaks), phosphorylated H3 (mitotic cells), translocated p53 (genotoxicity), and cleaved PARP1 (apoptosis). A reference dataset of 31 compounds with well-established MoA was studied using the MicroFlow(®) micronucleus assay...
September 21, 2017: Environmental and Molecular Mutagenesis
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