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Environmental and Molecular Mutagenesis

Jeffrey K Wickliffe, Stephen D Dertinger, Dorothea K Torous, Svetlana L Avlasevich, Bridget R Simon-Friedt, Mark J Wilson
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...
October 14, 2016: Environmental and Molecular Mutagenesis
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 Tanir, Veronique Thybaud, Jan van Benthem, Carole L Yauk, Errol Zeiger, Mirjam Luijten
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...
September 21, 2016: Environmental and Molecular Mutagenesis
George R Hoffmann, Michael D Shelby, Errol Zeiger
No abstract text is available yet for this article.
October 2016: Environmental and Molecular Mutagenesis
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
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 same geographic region...
October 2016: Environmental and Molecular Mutagenesis
Margherita Tussellino, Raffaele Ronca, Rosa Carotenuto, Maria M Pallotta, Maria Furia, Teresa Capriglione
Chlorpyrifos (CPF) is an organophosphate insecticide used primarily to control foliage and soil-borne insect pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce dose-related abnormalities such as slower brain growth and cerebral cortex thinning. In lower vertebrates, for example, fish and amphibians, teratogenic activity of this compound is correlated with several anatomical alterations. Little is known about the effects of CPF on mRNA expression of genes involved in early development of the anatomical structures appearing abnormal in embryos...
October 2016: Environmental and Molecular Mutagenesis
Vinita Chauhan, Byron Kuo, James P McNamee, Ruth C Wilkins, Carole L Yauk
Recent advances in "-omics" technologies have simplified capacity to concurrently assess expression profiles of thousands of targets in a cellular system. However, compilation and analysis of "omics" data in support of human health protection remains a challenge. Benchmark dose (BMD) modeling is currently being employed in chemical risk assessment to estimate acceptable levels of exposure. Although typically applied to conventional endpoints, newer software has enabled this application to be extended to transcriptomic datasets...
October 2016: Environmental and Molecular Mutagenesis
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
Erythrocyte-based PIG-A assay is sensitive and reliable in detecting exposure to mutagenetic agents in animal studies, but there are few data from human populations. 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 (RBC(CD59-) ) frequencies in 217 subjects from general population. The majority of subjects had a relatively low mutant frequencies (MFs) (average, 5.25 ± 3...
October 2016: Environmental and Molecular Mutagenesis
J P Wojciechowski, C R Gleason, D J Roberts, L L Custer
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...
October 2016: Environmental and Molecular Mutagenesis
Teng Zhang, Wei Shen, Massimo De Felici, Xi-Feng Zhang
Primordial follicle formation and the subsequent transition of follicles through primary and secondary stages constitute crucial events of oogenesis. In particular, in mammals, defects in the processes that precede and accompany the formation of the primordial follicle pool can affect the size of this population significantly, while alterations in follicle activation, growth and maturation can result in premature depletion of the follicle reserve or cause follicle arrest at immature stages. Over the last decade, in vitro and in vivo approaches have been used to provide evidence that exposure to di(2-ethylhexyl)phthalate(DEHP), the most widely used plasticizer, has a deleterious effect on various stages of folliculogenesis in rodents...
October 2016: Environmental and Molecular Mutagenesis
(no author information available yet)
No abstract text is available yet for this article.
September 2016: Environmental and Molecular Mutagenesis
Alexandra S Long, Margaret Watson, Volker M Arlt, Paul A White
Coal tar (CT) is a thick black liquid produced as a by-product of coal carbonization to produce coke or manufactured gas. It is comprised a complex mixture of polycyclic aromatic compounds, including a wide range of polycyclic aromatic hydrocarbons (PAHs), many of which are genotoxic and carcinogenic. CT is used in some pavement sealants (also known as sealcoat), which are applied to pavement in order to seal and beautify the surface. Human exposure is known to occur not only during application, but also as a result of the weathering process, as elevated levels of PAHs have been found in settled house dust in residences adjacent to CT-sealed surfaces...
August 2016: Environmental and Molecular Mutagenesis
Yongmin Liu, Eunwoo Shim Park, Alexander T Gibbons, Eric D Shide, Rao L Divi, Ruth A Woodward, Miriam C Poirier
Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother-to-child transmission of human immunodeficiency virus 1 (HIV-1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15-year old human) after exposure of the dams to human-equivalent in utero ARV exposure protocols. Pregnant patas dams (3-5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation...
August 2016: Environmental and Molecular Mutagenesis
Xiwa Zhao, Xurui Wei, Lianmei Zhao, Li Shi, Jianxin Cheng, Shan Kang, Hui Zhang, Jun Zhang, Li Li, Haibo Zhang, Wei Zhao
The single nucleotide polymorphism (SNP) rs6983267 and cancer-associated region long non-coding RNA (CARLo-5) are associated with various human cancers. This study aimed to investigate the expression of CARLo-5 in endometrial carcinoma (EC) and its relationship with clinicopathological features and patient survival. The association of the rs6983267 SNP with EC risk and its involvement in the regulation of CARLo-5 expression in EC were investigated. The rs6983267 SNP was genotyped by polymerase chain reaction (PCR) and ligase detection reaction in 543 EC patients and 584 controls...
August 2016: Environmental and Molecular Mutagenesis
Francine I Vacchi, Josiane A S Vendemiatti, Vanessa Brosselin, Bianca Ferreira da Silva, Maria Valnice B Zanoni, Michel DeMeo, Sylvie Bony, Alain Devaux, Gisela A Umbuzeiro
Waters receiving textile discharges can exhibit genotoxic and mutagenic activity, which has been related to the presence of dyes and aromatic amines as synthesis precursors or byproducts. The aim of this study was to identify dyes and aromatic amines in water samples impacted by textile discharges, and to evaluate the genotoxic responses of these samples using the Salmonella/microsome assay in strains TA98 and YG1041, and the Fpg-modified comet assay in the RTL-W1 fish cell line. The genotoxicity of river samples downstream of the discharge was greater than the upstream samples in both of the Ames tests...
August 2016: Environmental and Molecular Mutagenesis
Derek T Bernacki, Steven M Bryce, Jeffrey C Bemis, David Kirkland, Stephen D Dertinger
Previous work with a diverse set of reference chemicals suggests that an in vitro multiplexed flow cytometry-based assay (MultiFlow™ DNA Damage Kit-p53, γH2AX, Phospho-Histone H3) can distinguish direct-acting clastogens and aneugens from nongenotoxicants (Bryce SM et al. []: Environ Mol Mutagen 57:171-189). This work extends this line of investigation to include compounds that require metabolic activation to form reactive electrophiles. For these experiments, TK6 cells were exposed to 11 promutagens and 37 presumed nongenotoxicants in 96 well plates...
August 2016: Environmental and Molecular Mutagenesis
Miriam C Poirier
Over two centuries ago, Sir Percival Pott, a London surgeon, published a pioneering treatise showing that soot exposure was the cause of high incidences of scrotal cancers occurring in young men who worked as chimney sweeps. Practicing at a time when cellular pathology was not yet recognized, Sir Percival nonetheless observed that the high incidence and short latency of the chimney sweep cancers, was fundamentally different from the rare scrotal cancers typically found in elderly men. Furthermore, his diagnosis that the etiology of these cancers was related to chimney soot exposure, was absolutely accurate, conceptually novel, and initiated the field of "occupational cancer epidemiology...
August 2016: Environmental and Molecular Mutagenesis
Rogelio Recio-Vega, Tania González-Cortes, Edgar Olivas-Calderón, R Clark Lantz, A Jay Gandolfi, Gladis Michel-Ramirez
Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured...
August 2016: Environmental and Molecular Mutagenesis
M H Yashavarddhan, Sandeep K Shukla, Nitya N Srivastava, Mrutyunjay Suar, Sangeeta Dutta, Bhargab Kalita, Rajiv Ranjan, Abhinav Singh, Sania Bajaj, Manju L Gupta
DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure...
July 2016: Environmental and Molecular Mutagenesis
Caren Weinhouse, Maureen A Sartor, Christopher Faulk, Olivia S Anderson, Karilyn E Sant, Craig Harris, Dana C Dolinoy
Developmental exposure to the endocrine-active compound bisphenol A (BPA) has been linked to epigenotoxic and potential carcinogenic effects in rodent liver, prostate, and mammary glands. A dose-dependent increase in hepatic tumors in 10-month mice perinatally exposed to one of three doses of BPA (50 ng, 50 µg, or 50 mg BPA/kg chow) was previously reported. These tumors represent early-onset disease and lack classical sexual dimorphism in incidence. Here, adult epigenome-wide liver DNA methylation profiles to identify gene promoters associated with perinatal BPA exposure and disease in 10-month mice with and without liver tumors were investigated...
July 2016: Environmental and Molecular Mutagenesis
Myron F Goodman
The simplest forms of mutations, base substitutions, typically have negative consequences, aside from their existential role in evolution and fitness. Hypermutations, mutations on steroids, occurring at frequencies of 10(-2) -10(-4) per base pair, straddle a domain between fitness and death, depending on the presence or absence of regulatory constraints. Two facets of hypermutation, one in Escherichia coli involving DNA polymerase V (pol V), the other in humans, involving activation-induced deoxycytidine deaminase (AID) are portrayed...
July 2016: Environmental and Molecular Mutagenesis
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