Environmental and Molecular Mutagenesis This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Direct quantification of gamma H2AX by cell ‐based high throughput screening for evaluation of genotoxicity of pesticides in a human thyroid cell lines
Genotoxicity is thought to be the cause of many cancers. Genotoxicity due to environmental toxins may be partly responsible for the dramatic increase in the incidence of papillary thyroid cancer over the past two decades. Here, we present a fully automatable assay platform that directly quantifies the phosphorylation of nuclear histone gamma H2AX (γH2AX), a specific cellular marker for DNA double strand breaks (DSBs) via immunohistochemistry and laser scanning cytometry. It multiplexes γH2AX with total cell number measured as propidium iodide and calculates the percentage of cells with DSBs. Validation of this assay usin...
Source: Environmental and Molecular Mutagenesis - June 1, 2017 Category: Molecular Biology Authors: Jerome M. Hershman, Bryan France, Kevin Hon, Robert Damoiseaux Tags: Research Article Source Type: research

Association of cytochrome P450 1B1 haplotypes with head and neck cancer risk
This study used a case–control approach in North Indian population to determine associations between genetic variants in CYP1B1 and risk of Head and Neck Squamous Cell Carcinoma (HNSCC). We examined the genotype and haplotype frequencies at various single‐nucleotide polymorphisms (SNPs), including SNPs previously reported in the promoter region and intron 1 of CYP1B1 in Caucasians. Using cycle sequencing, 9 SNPs were identified in the promoter region, intron 1, and exons 2 and 3. Haplotype analysis revealed that 5 SNPs (those in the promoter region, intron, and Arg48Gly and Ala119Ser in exon 2) were in strong linkage d...
Source: Environmental and Molecular Mutagenesis - May 28, 2017 Category: Molecular Biology Authors: Tridiv Katiyar, Shailendra S. Maurya, Feza Hasan, Arvind P. Singh, Anwar J. Khan, Rahat Hadi, Sudhir Singh, Madan L.B. Bhatt, Devendra Parmar Tags: Research Article Source Type: research

Genotoxicity testing approaches for the safety assessment of substances used in food contact materials prior to their authorization in the European Union
In this study, we provide an analysis of the data on genotoxicity testing gathered by EFSA on food contact materials for the period 1992–2015. We also illustrate practical examples of the approaches that EFSA took when evaluating “non standard” food contact chemicals (e.g., polymeric additives, oligomer or other reaction mixtures, and nanosubstances). Additionally, EFSA's experience gained from using non testing methods and/or future possibilities in this area are discussed. Environ. Mol. Mutagen., 2017. © 2017 Wiley Periodicals, Inc. (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - May 28, 2017 Category: Molecular Biology Authors: Claudia Bolognesi, Anna F. Castoldi, Riccardo Crebelli, Eric Barth élémy, Daniela Maurici, Detlef Wölfle, Katharina Volk, Laurence Castle Tags: Review Source Type: research

Global regulatory requirements for mutagenicity assessment in the registration of industrial chemicals
Mutagenicity is an important toxicological endpoint that requires thorough evaluation during the industrial chemical registration process. Regulatory requirements for mutagenicity assessment in registration of industrial chemicals vary in geographic regions (and in some cases by intended application). Here we compile the mutagenicity testing requirements for registration of industrial chemicals from representative geographic regions (in alphabetical order), that is Australia, Brazil, Canada, China, European Union (EU), India, Japan, South Korea, Taiwan, and United States (US). We further discuss the challenges that industr...
Source: Environmental and Molecular Mutagenesis - May 25, 2017 Category: Molecular Biology Authors: Zhiying Ji, Nicholas S. Ball, Matthew J. LeBaron Tags: Review Source Type: research

Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances
This article reviews the classification criteria for germ cell mutagenicity and carcinogenicity and how they are applied to substances with evidence of mutagenicity. The implications and suitability of such a classification for hazard communication, risk assessment, and risk management are discussed. It is proposed that genotoxicity assessments should not focus on specifically identifying germ cell mutagens, particularly given the challenges associated with communicating this information in a meaningful way. Rather the focus should be on deriving data to characterize the mode of action and for use in the risk assessment of...
Source: Environmental and Molecular Mutagenesis - May 9, 2017 Category: Molecular Biology Authors: Nicholas S. Ball, Heli M. Hollnagel Tags: Commentary Source Type: research

Association between genetic variants in the promoter region of a novel antisense long noncoding RNA RP11 ‐392P7.6 and colorectal cancer risk
There is a widespread occurrence of antisense transcripts' regulation on cancer‐related genes in cancer biology. RP11‐392P7.6 is antisense to the coding region of cancer‐related gene GPRC5D, which has been found recently. The aim of this study was to investigate the associations of tagSNPs in the promoter region of RP11‐392P7.6 with the risk of colorectal cancer. We conducted a two‐stage case–control study, with a discovery set (320 cases and 319 controls) and a validation set (501 cases and 538 controls). Four tagSNPs (rs1531970, rs1642199, rs4763903, and rs10845671) were selected based on 1000 Genomes Project...
Source: Environmental and Molecular Mutagenesis - May 1, 2017 Category: Molecular Biology Authors: Mingjuan Jin, Simeng Gu, Ding Ye, Yingjun Li, Fangyuan Jing, Qilong Li, Kun Chen Tags: Research Article Source Type: research

Safety assessment and global regulatory requirements for genetic toxicity evaluations of medical devices
Medical devices have the potential to leach substances which, depending on the contact category of the device, can directly contact the human body. Hence, appropriate evaluation for genetic toxicity as part of the biocompatibility risk assessment is critical. The biocompatibility risk assessment of medical devices is guided by the ISO 10993 series of standards. The recently revised ISO 10993‐3 (2014) provides guidance on evaluating the genotoxicity, carcinogenicity and reproductive toxicity potential of medical devices. The revised standard includes the use of risk assessments and chemical characterization in addition to...
Source: Environmental and Molecular Mutagenesis - May 1, 2017 Category: Molecular Biology Authors: Robert T. Przygoda Tags: Review Source Type: research

Cytotoxic and genotoxic effects of 131I and 60Co in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid ‐stimulating hormone treatment
Normally, differentiated thyroid cancer (DTC) tends to be biologically indolent, highly curable and has an excellent prognosis. However, the treatment may fail when the cancer has lost radioiodine avidity. The present study was carried out in order to evaluate the cytotoxic and genotoxic effects of 131I and 60Co and radioiodine uptake in WRO cells, derived from DTC, harboring the BRAFV600E mutation. WRO cells showed a relatively slow cell cycle of 96.3 h with an unstable karyotype containing various double minutes. The genotoxicity assay (micronucleus test) showed a relative high radioresistance to 131I (0.07–3.70 MBq/mL...
Source: Environmental and Molecular Mutagenesis - May 1, 2017 Category: Molecular Biology Authors: Fl ávia Gomes Silva Valgôde, Márcia Augusta da Silva, Daniel Perez Vieira, Maria Teresa Carvalho Pinto Ribela, Paolo Bartolini, Kayo Okazaki Tags: Research Article Source Type: research

Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood
We examined the association between in utero phthalate exposure and altered patterns of cord blood DNA methylation in 336 Mexican‐American newborns. Concentrations of 11 phthalate metabolites were analyzed in maternal urine samples collected at 13 and 26 weeks gestation as a measure of fetal exposure. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. To identify differentially methylated regions (DMRs) that may be more informative than individual CpG sites, we used two different approaches, DMRcate and comb‐p. Regional assessment by both methods id...
Source: Environmental and Molecular Mutagenesis - May 1, 2017 Category: Molecular Biology Authors: Olivia Solomon, Paul Yousefi, Karen Huen, Robert B. Gunier, Maria Escudero ‐Fung, Lisa F. Barcellos, Brenda Eskenazi, Nina Holland Tags: Research Article Source Type: research

Prenatal environmental tobacco smoke exposure increases allergic asthma risk with methylation changes in mice
Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen‐induced murine model. Pregnant C57BL/6 mice were exposed to either filtered air or ETS during gestation, and their offspring were further exposed to HDM at 6–7 weeks old to induce allergic inflammation. Me...
Source: Environmental and Molecular Mutagenesis - May 1, 2017 Category: Molecular Biology Authors: Sonja Christensen, Zeina Jaffar, Elizabeth Cole, Virginia Porter, Maria Ferrini, Britten Postma, Kent E. Pinkerton, Mihi Yang, Yang Jee Kim, Luke Montrose, Kevan Roberts, Andrij Holian, Yoon Hee Cho Tags: Research Article Source Type: research

Mechanisms of DNA damage, repair, and mutagenesis
Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease‐states. However, robust DNA repair and damage‐bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine‐tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating t...
Source: Environmental and Molecular Mutagenesis - May 1, 2017 Category: Molecular Biology Authors: Nimrat Chatterjee, Graham C. Walker Tags: Review Source Type: research

Induction of micronuclei and cell cycle arrest by some tri ‐ and tetrachlorobiphenyls in mammalian cells deficient in xenobiotic‐metabolizing enzymes
This study suggests that 2,3,4′‐ and 2,3,3′‐substituted PCBs are micronuclei inducers and G2/M arresters among a number of trichlorobiphenyls in mammalian cell lines, though with potency lower than that observed recently in V79‐derived cells expressing human CYP2E1. Similarly, some noncoplanar tetrachlorobiphenyls possess metabolism‐independent chromosome‐damaging potentials. Environ. Mol. Mutagen. 58:199–208, 2017. © 2017 Wiley Periodicals, Inc. (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - April 26, 2017 Category: Molecular Biology Authors: Haiyan Wang, Liwen Wei, Yifan Wu, Hansi Jia, Hao Jiang, Yungang Liu Tags: Research Article Source Type: research

Comparative tumor promotion assessment of e ‐cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay
In vitro cell transformation assays (CTA) are used to assess the carcinogenic potential of chemicals and complex mixtures and can detect nongenotoxic as well as genotoxic carcinogens. The Bhas 42 CTA has been developed with both initiation and promotion protocols to distinguish between these two carcinogen classes. Cigarette smoke is known to be carcinogenic and is positive in in vitro genotoxicity assays. Cigarette smoke also contains nongenotoxic carcinogens and is a tumour promoter and cocarcinogen in vivo. We have combined a suite of in vitro assays to compare the relative biological effects of new categories of tobacc...
Source: Environmental and Molecular Mutagenesis - April 26, 2017 Category: Molecular Biology Authors: Damien Breheny, Oluwatobiloba Oke, Kamala Pant, Marianna Ga ça Tags: Research Article Source Type: research

Issue Information
(Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - April 26, 2017 Category: Molecular Biology Tags: Issue Information Source Type: research

An in vitro system for measuring genotoxicity mediated by human CYP3A4 in Saccharomyces cerevisiae
P450 activity is required to metabolically activate many chemical carcinogens, rendering them highly genotoxic. CYP3A4 is the most abundantly expressed P450 enzyme in the liver, accounting for most drug metabolism and constituting 50% of all hepatic P450 activity. CYP3A4 is also expressed in extrahepatic tissues, including the intestine. However, the role of CYP3A4 in activating chemical carcinogens into potent genotoxins is unclear. To facilitate efforts to determine whether CYP3A4, per se, can activate carcinogens into potent genotoxins, we expressed human CYP3A4 in the DNA‐repair mutant (rad4 rad51) strain of budding ...
Source: Environmental and Molecular Mutagenesis - April 24, 2017 Category: Molecular Biology Authors: Michael Fasullo, Julian Freedland, Nicholas St. John, Cinzia Cera, Patricia Egner, Matthew Hartog, Xinxin Ding Tags: Research Article Source Type: research