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.

Transcriptomic responses in the oral cavity of F344 rats and B6C3F1 mice following exposure to Cr(VI): Implications for risk assessment
Exposure to hexavalent chromium [Cr(VI)] in drinking water was previously reported to increase oral tumor incidence in F344 rats. To investigate the mode of action for these tumors, transcriptomic profiles in oral mucosa samples of F344 rats and B6C3F1 mice were analyzed following exposure to 0.1–180 ppm Cr(VI) for 7 or 90 days. In rats, genome‐wide microarray analyses identified no significantly differentially expressed genes (DEGs) at either time point. In mice, 14 and 1 DEGs were respectively identified after 7 and 90 days of exposure. Therefore, relaxed statistical criteria were employed to identify potential DEGs ...
Source: Environmental and Molecular Mutagenesis - September 30, 2016 Category: Molecular Biology Authors: Chad M. Thompson, Julia E. Rager, Mina Suh, Caroline L. Ring, Deborah M. Proctor, Laurie C. Haws, Rebecca C. Fry, Mark A. Harris Tags: Research Article Source Type: research

Evaluation of the LacZ reporter assay in cryopreserved primary hepatocytes for In vitro genotoxicity testing
We examined the effect of cryopreservation on phenotype and metabolic capacity of the LacZ hepatocytes, and assessed the predictive performance of the assay by testing a set of substances comprising true positive, true negative, and misleading positive substances. Additionally, a historical negative control database was created and the type of mutations induced was analyzed for two of the substances tested. Our findings indicate that proliferating cryopreserved primary hepatocytes derived from LacZ plasmid mice retain their hepatocyte‐specific characteristics and metabolic competence. Furthermore, we demonstrate that bot...
Source: Environmental and Molecular Mutagenesis - September 30, 2016 Category: Molecular Biology Authors: Mirjam Luijten, Edwin P. Zwart, Martijn E.T. Doll é, Maaike de Pooter, Julie A. Cox, Paul A. White, Jan van Benthem Tags: Research Article Source Type: research

Human T lymphocytes bioactivate heterocyclic aromatic amines by forming DNA adducts
In this study, we investigated the ability of human T lymphocytes activated with PMA/Ionomycin or CD3/CD28 to express functional CYP1 activity and bioactivate three major HAA: 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), and 2‐amino‐9H‐pyrido[2,3‐b]indole (AαC) to form DNA adducts. Adducts were measured by ultraperformance liquid chromatography‐electrospray ionization/multistage scan mass spectrometry. The highest level of DNA adducts occurred for AαC (16 adducts per 109 nucleotides), followed by PhIP (9 adducts per 109 nucleo...
Source: Environmental and Molecular Mutagenesis - September 30, 2016 Category: Molecular Biology Authors: Medjda Bellamri, Ludovic Le Hegarat, Laurent Vernhet, Georges Baffet, Robert J. Turesky, Sophie Langou ët Tags: Research Article Source Type: research

In Vivo Pig ‐a gene mutation assay: Guidance for 3Rs‐friendly implementation
The rodent Pig‐a assay is an in vivo method for the detection of gene mutation, where lack of glycosylphosphatidylinositol‐anchored proteins on the surface of circulating red blood cells (RBCs) serves as a reporter for Pig‐a gene mutation. In the case of rats, the frequency of mutant phenotype RBCs is measured via fluorescent anti‐CD59 antibodies and flow cytometry. The Pig‐a assay meets the growing expectations for novel approaches in animal experimentation not only focusing on the scientific value of the assay but also on animal welfare aspects (3Rs principles), for example, amenable to integration into pivotal...
Source: Environmental and Molecular Mutagenesis - September 30, 2016 Category: Molecular Biology Authors: Marian Raschke, Bernd ‐W. Igl, Julia Kenny, Joanne Collins, Stephen D. Dertinger, Carson Labash, Javed A. Bhalli, Cameron C.M. Tebbe, Kylie M. McNeil, Andreas Sutter Tags: Research Article Source Type: research

Diet ‐induced obesity increases the frequency of Pig‐a mutant erythrocytes in male C57BL/6J mice
Obesity increases the risk of a number of chronic diseases in humans including several cancers. Biological mechanisms responsible for such increased risks are not well understood at present. Increases in systemic inflammation and oxidative stress, endogenous production of mutagenic metabolites, altered signaling in proliferative pathways, and increased sensitivity to exogenous mutagens and carcinogens are some of the potential contributing factors. We hypothesize that obesity creates an endogenously mutagenic environment in addition to increasing the sensitivity to environmental mutagens. To test this hypothesis, we examin...
Source: Environmental and Molecular Mutagenesis - September 30, 2016 Category: Molecular Biology Authors: Jeffrey K. Wickliffe, Stephen D. Dertinger, Dorothea K. Torous, Svetlana L. Avlasevich, Bridget R. Simon ‐Friedt, Mark J. Wilson Tags: Research Article Source Type: research

Chlorpyrifos exposure affects fgf8, sox9, and bmp4 expression required for cranial neural crest morphogenesis and chondrogenesis in Xenopus laevis embryos
This study investigated the effects of exposure to different CPF concentrations (10, 15 and 20 mg/L) on Xenopus laevis embryos from stage 4/8 to stage 46. Some of the morphological changes we detected in CPF‐exposed embryos included cranial neural crest cell (NCC)‐derived structures. For this reason, we analyzed the expression of select genes involved in hindbrain patterning (egr2), cranial neural crest chondrogenesis, and craniofacial development (fgf8, bmp4, sox9, hoxa2 and hoxb2). We found that CPF exposure induced a reduction in transcription of all the genes involved in NCC‐dependent chondrogenesis, with largest...
Source: Environmental and Molecular Mutagenesis - September 26, 2016 Category: Molecular Biology Authors: Margherita Tussellino, Raffaele Ronca, Rosa Carotenuto, Maria M. Pallotta, Maria Furia, Teresa Capriglione Tags: Research Article Source Type: research

Di(2 ‐ethylhexyl)phthalate: Adverse effects on folliculogenesis that cannot be neglected
This article reviews the evidence, with particular reference to our own findings, that DEHP may actually exert a variety of adverse effects on mammalian folliculogenesis from early to final stages of oogenesis, including altered development of the primordial germ cells, impaired fetal oocyte survival and meiotic progression, reduced oocyte nest breakdown, acceleration of primordial follicle activation, altered follicle steroidogenesis and increased follicle atresia. These effects can cause serious complications for reproductive and nonreproductive women's health. In addition, emerging data indicate that phthalates, includi...
Source: Environmental and Molecular Mutagenesis - August 16, 2016 Category: Molecular Biology Authors: Teng Zhang, Wei Shen, Massimo De Felici, Xi ‐Feng Zhang Tags: Review Source Type: research

Issue Information
(Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - August 8, 2016 Category: Molecular Biology Tags: Issue Information Source Type: research

Remembering Heinrich Malling
(Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - July 31, 2016 Category: Molecular Biology Authors: George R. Hoffmann, Michael D. Shelby, Errol Zeiger Tags: In Memoriam Source Type: research

Effects of occupational exposure to carbon black on peripheral white blood cell counts and lymphocyte subsets
The International Agency for Research on Cancer has classified carbon black (CB) as a possible (Group 2B) human carcinogen. Given that most CB manufacturing processes result in the emission of various types of chemicals, it is uncertain if the adverse health effects that have been observed in CB‐exposed workers are related to CB specifically or are due to other exposures. To address this issue, we conducted a cross‐sectional molecular epidemiology study in China of 106 male factory workers who were occupationally exposed to pure CB and 112 unexposed male workers frequency‐matched by age and smoking status from the sa...
Source: Environmental and Molecular Mutagenesis - July 31, 2016 Category: Molecular Biology Authors: Yufei Dai, Yong Niu, Huawei Duan, Bryan A. Bassig, Meng Ye, Xiao Zhang, Tao Meng, Ping Bin, Xiaowei Jia, Meili Shen, Rong Zhang, Wei Hu, Xiaofa Yang, Roel Vermeulen, Debra Silverman, Nathaniel Rothman, Qing Lan, Shanfa Yu, Yuxin Zheng Tags: Research Article Source Type: research

Next generation testing strategy for assessment of genomic damage: A conceptual framework and considerations
For several decades, regulatory testing schemes for genetic damage have been standardized where the tests being utilized examined mutations and structural and numerical chromosomal damage. This has served the genetic toxicity community well when most of the substances being tested were amenable to such assays. The outcome from this testing is usually a dichotomous (yes/no) evaluation of test results, and in many instances, the information is only used to determine whether a substance has carcinogenic potential or not. Over the same time period, mechanisms and modes of action (MOAs) that elucidate a wider range of genomic d...
Source: Environmental and Molecular Mutagenesis - July 31, 2016 Category: Molecular Biology Authors: Kerry L. Dearfield, B. Bhaskar Gollapudi, Jeffrey C. Bemis, R. Daniel Benz, George R. Douglas, Rosalie K. Elespuru, George E. Johnson, David J. Kirkland, Matthew J. LeBaron, Albert P. Li, Francesco Marchetti, Lynn H. Pottenger, Emiel Rorije, Jennifer Y. T Tags: Review Source Type: research

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field
In this report, radiation data obtained from the Gene Expression Omnibus (GEO) were analyzed to generate BMD values for transcriptional responses. The datasets comprised microarray analyses of human blood gamma‐irradiated ex vivo (0–20 Gy) and human‐derived cell lines exposed to alpha particle radiation (0.5–1.5 Gy). The distributions of BMDs for statistically significant genes and pathways in response to radiation exposure were examined and compared across studies. BMD modeling could identify pathway/gene sensitivities across wide radiation dose ranges, experimental conditions (time‐points, cell types) and radia...
Source: Environmental and Molecular Mutagenesis - July 31, 2016 Category: Molecular Biology Authors: Vinita Chauhan, Byron Kuo, James P. McNamee, Ruth C. Wilkins, Carole L. Yauk Tags: Research Article Source Type: research

A population study using the human erythrocyte PIG ‐A assay
In this study, we employed a method for detecting CD59 phenotypic variants, resulting from mutation in the PIG‐A gene, in human red blood cells (RBCs), and determined the CD59‐deficient RBC (RBCCD59−) frequencies in 217 subjects from general population. The majority of subjects had a relatively low mutant frequencies (MFs) (average, 5.25 ± 3.6 × 10−6, median, 4.38 × 10−6, for all subjects), but with males having a significantly greater MFs (5.97 ± 4.0 × 10−6) than females (4.19 ± 2.5 ×10−6). There was no correlation between MFs and age. In addition, MFs showed no difference between smoker a...
Source: Environmental and Molecular Mutagenesis - July 31, 2016 Category: Molecular Biology Authors: Yiyi Cao, Li Yang, Nannan Feng, Oumin Shi, Jing Xi, Xinyue You, Chunrong Yin, Huan Yang, Katsuyoshi Horibata, Masamitsu Honma, Biyun Qian, Wei Weng, Yang Luan Tags: Research Article Source Type: research

Novel statistical approach for evaluating flow cytometric in vitro micronucleus data
Statistical methods currently recommended for analysis of in vitro micronucleus data are based on small sample sizes. The tests are designed to evaluate linear trends and differences between treated and control samples. When using flow cytometric analysis, >5 times the number of cells are easily evaluated, and the variance estimates from these large samples are small. Application of these recommended tests to large samples resulted in statistically significant outcomes which were not considered to be biologically meaningful. Alternative statistical methods for testing trends and differences among treatments that were ei...
Source: Environmental and Molecular Mutagenesis - July 31, 2016 Category: Molecular Biology Authors: J.P. Wojciechowski, C.R. Gleason, D.J. Roberts, L.L. Custer Tags: Research Article Source Type: research

Di(2 ‐ethylhexyl)phthalate: Adverse effects on folliculogenesis that cannot be negelected
This article reviews the evidence, with particular reference to our own findings, that DEHP may actually exert a variety of adverse effects on mammalian folliculogenesis from early to final stages of oogenesis, including altered development of the primordial germ cells, impaired fetal oocyte survival and meiotic progression, reduced oocyte nest breakdown, acceleration of primordial follicle activation, altered follicle steroidogenesis and increased follicle atresia. These effects can cause serious complications for reproductive and nonreproductive women's health. In addition, emerging data indicate that phthalates, includi...
Source: Environmental and Molecular Mutagenesis - July 31, 2016 Category: Molecular Biology Authors: Teng Zhang, Wei Shen, Massimo De Felici, Xi ‐Feng Zhang Tags: Review Source Type: research