Linking DNA adduct formation and human cancer risk in chemical carcinogenesis
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 no...
Source: Environmental and Molecular Mutagenesis - May 31, 2016 Category: Molecular Biology Authors: Miriam C. Poirier Tags: Review Source Type: research

γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate
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 Co60 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 follo...
Source: Environmental and Molecular Mutagenesis - May 31, 2016 Category: Molecular Biology Authors: M.H. Yashavarddhan, Sandeep K. Shukla, Nitya N. Srivastava, Mrutyunjay Suar, Sangeeta Dutta, Bhargab Kalita, Rajiv Ranjan, Abhinav Singh, Sania Bajaj, Manju L Gupta Tags: Research Article Source Type: research

Epigenome‐wide DNA methylation analysis implicates neuronal and inflammatory signaling pathways in adult murine hepatic tumorigenesis following perinatal exposure to bisphenol A
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 w...
Source: Environmental and Molecular Mutagenesis - May 31, 2016 Category: Molecular Biology Authors: Caren Weinhouse, Maureen A. Sartor, Christopher Faulk, Olivia S. Anderson, Karilyn E. Sant, Craig Harris, Dana C. Dolinoy Tags: Research Article Source Type: research

Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic
In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen., 2016. © 2016 Wiley Periodicals, Inc. (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - May 31, 2016 Category: Molecular Biology Authors: Rogelio Recio‐Vega, Tania González‐Cortes, Edgar Olivas‐Calderón, R. Clark Lantz, A. Jay Gandolfi, Gladis Michel‐Ramirez Tags: Research Article Source Type: research

Bacterial mutagenicity assays: Vehicle and positive control results from the standard Ames assay, the 6‐ and 24‐well miniaturized plate incorporation assays and the Ames II™ assay
Bacterial mutation assays are conducted routinely as part of the safety assessment of new chemicals. The OECD Test Guideline (TG) 471 describes the conduct of the standard agar plate Ames assay, required for regulatory submissions. Higher throughput non‐OECD 471 TG assays, such as the miniaturized plate incorporation and Ames II™ assays, can be used for prescreening purposes. We have compiled historical vehicle and positive control data generated using these methods. The historical database is comprised from experiments spanning 9 years and includes >1000 experiments from the standard Ames assay using the plate inco...
Source: Environmental and Molecular Mutagenesis - May 19, 2016 Category: Molecular Biology Authors: Kamala Pant, Shannon Bruce, Jamie Sly, Michelle Klug Laforce, Sandra Springer, Mark Cecil, Edgar Andrus, Emily Dakoulas, Valentine O. Wagner, Nicola J. Hewitt, Rohan Kulkarni Tags: Research Article Source Type: research

Better living with hyper‐mutation
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. Pol V is induced as part of the DNA‐damage‐induced SOS regulon, and is responsible...
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: Myron F. Goodman Tags: Review Source Type: research

Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of 56Fe particles
Exposures of brain tissue to ionizing radiation can lead to persistent deficits in cognitive functions and behaviors. However, little is known about the quantitative relationships between exposure dose and neurological risks, especially for lower doses and among genetically diverse individuals. We investigated the dose relationship for spatial memory learning among genetically outbred male Wistar rats exposed to graded doses of 56Fe particles (sham, 5, 10, 15, and 20 cGy; 1 GeV/n). Spatial memory learning was assessed on a Barnes maze using REL3 ratios measured at three months after exposure. Irradiated animals showed dose...
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: Andrew J. Wyrobek, Richard A. Britten Tags: Research Article Source Type: research

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n‐butoxyethylpyridylporphyrin‐based redox modifier
Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy‐induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE‐2‐PyP5+ (Mn(III)meso‐tetrakis(N‐n‐butoxyethylpyridinium ‐2‐yl)porphyrin) rescued RT‐induced white matter damage in cranially‐irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard‐of‐care for adult glioblastoma, whereas cisplatin is often used for treatment of ...
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: Douglas H. Weitzel, Artak Tovmasyan, Kathleen A. Ashcraft, Alina Boico, Samuel R. Birer, Kingshuk Roy Choudhury, James Herndon, Ramona M. Rodriguiz, William C. Wetsel, Katherine B. Peters, Ivan Spasojevic, Ines Batinic‐Haberle, Mark W. Dewhirst Tags: Research Article Source Type: research

Understanding and targeting dynamic stress responses of the brain: What we have learned and how to improve neurocognitive outcome following neurotoxic insult
(Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: Charles L. Limoli Tags: Editorial Source Type: research

A multi‐ingredient dietary supplement abolishes large‐scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice
Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF‐1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi‐ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age‐related physical deteri...
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: J.A. Lemon, V. Aksenov, R. Samigullina, S. Aksenov, W.H. Rodgers, C.D. Rollo, D.R. Boreham Tags: Research Article Source Type: research

Transcriptional profiling of the mouse hippocampus supports an NMDAR‐mediated neurotoxic mode of action for benzo[a]pyrene
Benzo[a]pyrene (BaP) is a genotoxic carcinogen and a neurotoxicant. The neurotoxicity of BaP is proposed to arise from either genotoxicity leading to neuronal cell death, or perturbed expression of N‐methyl‐d‐aspartate receptor (NMDAR) subunits. To explore these hypotheses, we profiled hippocampal gene expression of adult male Muta™Mouse administered 0, 1, 35, or 70 mg BaP/kg bw per day by oral gavage for 3 days. Transcriptional profiles were examined by RNA‐sequencing (RNA‐seq), DNA microarrays, and real‐time quantitative reverse transcription polymerase chain reaction (RT‐PCR). BaP‐DNA adducts in the ce...
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: Nikolai L. Chepelev, Alexandra S. Long, Wayne J. Bowers, Rémi Gagné, Andrew Williams, Byron Kuo, David H. Phillips, Volker M. Arlt, Paul A. White, Carole L. Yauk Tags: Research Article Source Type: research

No cytotoxicity or genotoxicity of graphene and graphene oxide in murine lung epithelial FE1 cells in vitro
Graphene and graphene oxide receive much attention these years, because they add attractive properties to a wide range of applications and products. Several studies have shown toxicological effects of other carbon‐based nanomaterials such as carbon black nanoparticles and carbon nanotubes in vitro and in vivo. Here, we report in‐depth physicochemical characterization of three commercial graphene materials, one graphene oxide (GO) and two reduced graphene oxides (rGO) and assess cytotoxicity and genotoxicity in the murine lung epithelial cell line FE1. The studied GO and rGO mainly consisted of 2–3 graphene layers wit...
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: Stefan Bengtson, Kirsten Kling, Anne Mette Madsen, Asger W. Noergaard, Nicklas Raun Jacobsen, Per Axel Clausen, Beatriz Alonso, Amaia Pesquera, Amaia Zurutuza, Raphael Ramos, Hanako Okuno, Jean Dijon, Håkan Wallin, Ulla Vogel Tags: Research Article Source Type: research

3D surface analysis of hippocampal microvasculature in the irradiated brain
This study demonstrates the utility of two distinct methodologies for quantifying these important adverse effects of radiotherapy. Environ. Mol. Mutagen., 2016. © 2016 Wiley Periodicals, Inc. (Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - April 30, 2016 Category: Molecular Biology Authors: Brianna M. Craver, Munjal M. Acharya, Barrett D. Allen, Sarah N. Benke, Nan W. Hultgren, Janet E. Baulch, Charles L. Limoli Tags: Research Article Source Type: research

Dr. William Francis (Bill) Morgan (1952–2015)
(Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - April 27, 2016 Category: Molecular Biology Authors: Jeffrey L. Schwartz Tags: In Memoriam Source Type: research

Issue Information
(Source: Environmental and Molecular Mutagenesis)
Source: Environmental and Molecular Mutagenesis - April 15, 2016 Category: Molecular Biology Tags: Issue Information Source Type: research