Article
Environmental Sciences
Yuzhi Chen, Mustafa Abbass, Trisha Brock, Gian Hobbs, Leonardo A. Ciufo, Christopher Hopkins, Volker M. Arlt, Stephen R. Stuerzenbaum
Summary: Polycyclic aromatic hydrocarbons (PAHs), including benzo [a]pyrene (BaP), are carcinogenic components of tobacco smoke. The toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1) in mammals, but absent in Caenorhabditis elegans. In worms, the CYP-35 enzyme family is induced after BaP exposure. BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner in C. elegans, while deletion of the cyp-35A2 gene increases neutral lipid metabolism. A dual-labelled reporter strain, cyp-35A2:mCherry;unc-47:GFP, helps identify upstream regulators elt-2, nhr-49, and fos-1 driving BaP metabolism in worms, making it a valuable resource for toxicology and lipid metabolism research.
ENVIRONMENTAL POLLUTION
(2023)
Article
Chemistry, Analytical
Li Liu, Maomin Peng, Ke Xu, Hong Xia, Xitian Peng, Lijun Peng, Jin Z. Zhang
Summary: Molecularly imprinted polymers with methylammonium lead halide perovskite quantum dots were prepared and used for the determination of benzo(a)pyrene. The interaction between MIP@MAPbBr(3) PQDs and BaP is a dynamic process, enhancing the PL intensity. The molecularly imprinted fluorescence assay shows good specificity and selectivity for BaP in complex mixtures.
Article
Environmental Sciences
Abigail DeBofsky, Yuwei Xie, Jonathan K. Challis, Phillip J. Ankley, Markus Brinkmann, Paul D. Jones, John P. Giesy
Summary: The study investigated the effects of BaP on the active gut microbiome of juvenile fathead minnows, finding that BaP reduces microbiome diversity, alters community composition, and leads to differential proportions of taxa associated with hydrocarbon degradation and fish health. The results also indicated ecological resistance and/or resilience of gut microbiota to BaP exposure.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Biotechnology & Applied Microbiology
Danielle P. M. LeBlanc, Matthew Meier, Fang Yin Lo, Elizabeth Schmidt, Charles Valentine, Andrew Williams, Jesse J. Salk, Carole L. Yauk, Francesco Marchetti
Summary: Exposure to environmental mutagens increases the risk of cancer and genetic disorders. Using Duplex Sequencing (DS) technology, this study analyzed mutation induction in the bone marrow of MutaMouse males exposed to benzo(a)pyrene (BaP). The results revealed a linear dose-related induction of mutations across all targets, with heterochromatic and intergenic regions exhibiting the highest mutation frequencies. The types of mutations enriched in BaP-exposed mice were consistent with the known etiology of BaP mutagenesis. Furthermore, DS showed a positive correlation with the gold-standard transgenic rodent gene mutation assay.
Article
Environmental Sciences
Abigail DeBofsky, Yuwei Xie, Jonathan K. Challis, Niteesh Jain, Markus Brinkmann, Paul D. Jones, John P. Giesy
Summary: The study showed that environmentally-relevant concentrations of BaP can alter the diversity of the gut microbiome and community network connectivity. Exposure to BaP reduced alpha diversity at the greatest exposure concentrations, but also altered community composition and reduced network complexity of the microbial community.
ENVIRONMENTAL POLLUTION
(2021)
Article
Chemistry, Analytical
Jingjing Yao, Xinxin Xu, Liqiang Liu, Hua Kuang, Zhengyou Wang, Chuanlai Xu
Summary: This study developed a sensitive and broadly specific icELISA and GNP-ICS assay for the detection of B[a]P, demonstrating their reliability in edible oil samples.
Review
Plant Sciences
Philomena Chu, Sarah Zanon Agapito-Tenfen
Summary: Classical genetic engineering and new genome editing techniques, especially CRISPR/Cas technology, have increased the possibilities for modifying genetic material in organisms, potentially offering novel agricultural traits. However, concerns arise from unintended genetic modifications reported as side-effects. This systematic review of scientific literature on unintended genomic alterations in plants modified through various techniques reveals a wide range of effects, from small nucleotide polymorphisms to large structural variations, with a potential underestimation due to limited use of comprehensive sequencing methods. Future research should focus on more thorough examination of analytical methods to provide regulators with valuable information for detection and identification of genomic interventions.
Article
Chemistry, Physical
Xiaopeng Wang, Noa Marom
Summary: Optical upconversion using TTA emitters allows for efficient photon harvesting in solar cells. We used energetic criteria and computer simulations to identify promising TTA emitters. These methods can be used to discover and design more high-performance TTA emitters efficiently.
MOLECULAR SYSTEMS DESIGN & ENGINEERING
(2022)
Article
Toxicology
Annette E. Dodge, Danielle P. M. LeBlanc, Gu Zhou, Andrew Williams, Matthew J. Meier, Phu Van, Fang Yin Lo, Charles C. Valentine, Jesse J. Salk, Carole L. Yauk, Francesco Marchetti
Summary: Duplex Sequencing (DS) is a high-accuracy DNA sequencing technology that has advantages over conventional mutagenicity assays. In this study, DS was used to analyze mutations induced by procarbazine (PRC) in mouse bone marrow. DS detected significant increases in mutation frequencies and changes to mutation spectra at different PRC doses, demonstrating its superiority over classical mutagenicity assays.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Environmental Sciences
Junjun Ling, Yuhong Wang, Lihai Ma, Yu Zheng, Hongqu Tang, Lingzhan Meng, Liang Zhang
Summary: The study revealed that KIF11 may be a key gene in BPDE-related lung cancer, and its overexpression is associated with the advanced stage and poor prognosis of lung cancer. Therefore, KIF11 might be a potential target for the prevention and therapy of BPDE-induced lung cancer.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alissa Drees, Markus Fischer
Summary: The HiTS-FLIP technology improves the efficiency of aptamer selection, providing insights into the relationship between sequence, structure, and function, which supports the evolution of aptamers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Margherita Bernardeschi, Patrizia Guidi, Mara Palumbo, Massimo Genovese, Michela Alfe, Valentina Gargiulo, Paolo Lucchesi, Vittoria Scarcelli, Alessandra Falleni, Elisa Bergami, Francesca S. Freyria, Barbara Bonelli, Ilaria Corsi, Giada Frenzilli
Summary: The study focused on using non-genotoxic nanoparticles to reduce the genetic and chromosomal damage associated with exposure to Benzo(a)pyrene (B(a)P). The results showed that pure Anatase n-TiO2 was the most suitable material, as it is cytotoxicity and genotoxicity free and able to reduce the genetic and chromosomal damage caused by B(a)P exposure.
Article
Biochemistry & Molecular Biology
Mohammad A. Alzohairy, Amjad Ali Khan, Mohammed A. Alsahli, Saleh A. Almatroodi, Arshad Husain Rahmani
Summary: This study demonstrated that thymoquinone (TQ) has significant therapeutic effects against Benzopyrene (B(a)P)-induced lung injury, including reducing lipid profile, inflammatory markers, oxidative stress, and increasing antioxidant enzyme levels, as well as decreasing apoptosis rate.
Article
Microbiology
Ying Bai, Lynn M. Osikowicz, Andrias Hojgaard, Rebecca J. Eisen
Summary: In this study, a quadruplex PCR amplicon sequencing assay using next-generation sequencing technology was developed to accurately and rapidly detect and differentiate Bartonella species. The assay demonstrated high specificity and accuracy in differentiating Bartonella species in various tissue types.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Medical Laboratory Technology
Rebecca C. Allsopp, Karen Page, Bana Ambasager, Marc K. Wadsley, Emmanuel Acheampong, Tumisang P. Ntereke, Qi Guo, Gurdeep Matharu Lall, Kelly L. T. Gleason, Evie Wren, Georgios Nteliopoulos, Amelia J. Rushton, R. Charles Coombes, Jacqueline A. Shaw
Summary: A workflow for screening somatic copy number alterations (sCNAs) using picogram amounts of cell-free DNA (cfDNA) and single circulating tumor cells (CTCs) in breast cancer has been presented. The results showed that sCNAs were detected in the majority of metastatic breast cancer (MBC) patients' cfDNA and CTCs. Patients with detectable tumor fraction and OncomineTM variants had significantly lower overall survival rates. This approach could guide treatment decisions, support future trial designs, and enable remote monitoring.
CLINICAL CHEMISTRY
(2023)
Article
Toxicology
Byron Kuo, Marc A. Beal, John W. Wills, Paul A. White, Francesco Marchetti, Andy Nong, Tara S. Barton-Maclaren, Keith Houck, Carole L. Yauk
Summary: Risk assessments are increasingly relying on in vitro assays for genotoxicity testing. This study evaluated 292 chemical datasets using the in vitro micronucleus test (MNvit) for hazard identification. The results identified 157 clastogenic chemicals, 25 negatives, and 110 inconclusive substances. In vitro to in vivo extrapolation (IVIVE) was used to convert concentrations into administered equivalent doses (AEDs), which were generally lower than points of departure (PODs) based on in vivo endpoints. Exposure estimates were utilized to calculate bioactivity exposure ratio (BER) values, identifying chemicals that may require additional testing.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Environmental Sciences
Marc A. A. Beal, Marc Audebert, Tara Barton-Maclaren, Hannah Battaion, Jeffrey C. C. Bemis, Xuefei Cao, Connie Chen, Stephen D. D. Dertinger, Roland Froetschl, Xiaoqing Guo, George Johnson, Giel Hendriks, Laure Khoury, Alexandra S. S. Long, Stefan Pfuhler, Raja S. S. Settivari, Shamika Wickramasuriya, Paul White
Summary: Genotoxicity assessment plays a crucial role in chemical development and evaluation. Traditional assays have limitations in hazard classification and quantifying toxicity. Novel high-throughput in vitro assays offer a powerful approach for potency ranking and risk assessment. In this study, the use of in vitro to in vivo extrapolation models demonstrated protective dose levels for 20 out of 31 chemicals, indicating the potential of this testing strategy in enhancing prioritization and risk assessment of genotoxic chemicals.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2023)
Article
Environmental Sciences
Nikolai Chepelev, Alexandra S. S. Long, Marc Beal, Tara Barton-Maclaren, George Johnson, Kerry L. Dearfield, Daniel J. Roberts, Jan van Benthem, Paul White
Summary: Carcinogenicity and mutagenicity of 48 compounds were evaluated using a benchmark dose (BMD)-based approach and human exposure data. The study calculated margin of exposure values (MOEs) derived from carcinogenicity and genotoxicity to prioritize substances for risk management. Out of the 48 compounds, 16 had MOEs below 10,000 and were flagged for regulatory concern, with 15 being highlighted based on genotoxicity-derived MOEs. Transgenic rodent (TGR) mutagenicity data yielded similar regulatory decisions as carcinogenicity-derived MOEs for 10 out of 12 compounds analyzed. The study also examined the impact of benchmark response (BMR) on MOE determination and found that a higher BMR would result in missing compounds prioritized using default BMR. The findings suggest that genotoxicity data can effectively prioritize substances in the absence of carcinogenicity data, and highlight the need for reliable human exposure estimates and consensus on appropriate BMRs for genotoxicity endpoints.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2023)
Article
Toxicology
Geronimo Matteo, Karen Leingartner, Andrea Rowan-Carroll, Matthew Meier, Andrew Williams, Marc A. Beal, Matthew Gagne, Reza Farmahin, Shamika Wickramasuriya, Anthony J. F. Reardon, Tara Barton-Maclaren, J. Christopher Corton, Carole L. Yauk, Ella Atlas
Summary: Since 2010, BPA has been replaced by alternative chemicals in Canada. However, many of these chemicals lack sufficient data for toxicological risk assessment. In this study, high-throughput transcriptomics was used to assess the hazards of BPA and 15 alternative chemicals in breast cancer cells. The results indicate that several BPA alternative chemicals may cause similar hazards at similar concentrations to BPA, highlighting the importance of transcriptomic profiling for risk assessment of data-poor chemicals.
TOXICOLOGICAL SCIENCES
(2023)
Article
Toxicology
Annette E. Dodge, Danielle P. M. LeBlanc, Gu Zhou, Andrew Williams, Matthew J. Meier, Phu Van, Fang Yin Lo, Charles C. Valentine, Jesse J. Salk, Carole L. Yauk, Francesco Marchetti
Summary: Duplex Sequencing (DS) is a high-accuracy DNA sequencing technology that has advantages over conventional mutagenicity assays. In this study, DS was used to analyze mutations induced by procarbazine (PRC) in mouse bone marrow. DS detected significant increases in mutation frequencies and changes to mutation spectra at different PRC doses, demonstrating its superiority over classical mutagenicity assays.
ARCHIVES OF TOXICOLOGY
(2023)
Review
Environmental Sciences
Stephen D. Dertinger, Dingzhou Li, Carol Beevers, George R. Douglas, Robert H. Heflich, David P. Lovell, Daniel J. Roberts, Robert Smith, Yoshifumi Uno, Andrew Williams, Kristine L. Witt, Andreas Zeller, Changhui Zhou
Summary: Historical negative control data (HCD) have become increasingly important in interpreting genotoxicity test results. The workgroup of the International Workshops for Genotoxicity Testing provides recommendations on evaluating and using HCD to interpret study results. The findings support the use of HCD for data interpretation, but suggest a more flexible application considering the quality of the HCD.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2023)
Article
Biology
Vinita Chauhan, Jihang Yu, Ngoc Vuong, Lynne T. T. Haber, Andrew Williams, Scott S. S. Auerbach, Danielle Beaton, Yi Wang, Robert Stainforth, Ruth C. C. Wilkins, Edouard I. I. Azzam, Richard B. B. Richardson, Md Gulam Musawwir Khan, Ashok Jadhav, Julie J. J. Burtt, Julie Leblanc, Kristi Randhawa, Knut Erik Tollefsen, Carole L. L. Yauk
Summary: Exposure to different forms of ionizing radiation is common in various settings, and improving the accuracy of health risk estimation is crucial. Benchmark dose (BMD) modeling, commonly used in chemical hazard assessments, shows potential in the radiation field. It involves fitting mathematical models to dose-response data and identifying a point of departure. A workshop was organized to introduce radiation scientists to BMD modeling and its practical application, aiming to explore its usefulness in interpreting dose-response data and supporting regulatory decisions.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Biographical-Item
Genetics & Heredity
Carole Yauk
Article
Toxicology
Gregory C. Addicks, Andrea Rowan-Carroll, Anthony J. F. Reardon, Karen Leingartner, Andrew Williams, Matthew J. Meier, Ivy Moffat, Richard Carrier, Luigi Lorusso, Barbara A. Wetmore, Carole L. Yauk, Ella Atlas
Summary: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals that result in direct human exposure through various products. This study investigates the transcriptomic potency of PFAS mixtures using gene expression data from liver cell spheroids exposed to single PFAS and mixture exposures. The results suggest that the effects of PFAS mixtures on gene expression largely follow the predicted response through concentration addition, indicating absence of strong synergistic or antagonistic effects.
TOXICOLOGICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Mercedes Rose, Alain Filiatreault, Andrew Williams, Josee Guenette, Errol M. Thomson
Summary: Air pollution is associated with increased risk of metabolic diseases such as type 2 diabetes due to the dysregulation of the insulin-signaling pathway. This study aimed to investigate the effects of ozone on insulin-signaling genes in major metabolic tissues and explore the role of glucocorticoids. Results showed that ozone inhalation led to distinct mRNA profiles and altered phosphorylation states of insulin-signaling proteins, indicating tissue-specific regulation of insulin-signaling pathway genes through glucocorticoid-dependent and independent mechanisms.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Silvia Aidee Solorio-Rodriguez, Andrew Williams, Sarah Sos Poulsen, Kristina Bram Knudsen, Keld Alstrup Jensen, Per Axel Clausen, Pernille Hogh Danielsen, Hakan Wallin, Ulla Vogel, Sabina Halappanavar
Summary: This study aimed to determine the influence of single or multi-walled structures and surface functionalization on pulmonary toxicity of carbon nanotubes (CNTs) and to identify the underlying mechanisms. Mice were exposed to different doses of SWCNTs or MWCNTs, and inflammation and DNA damage were assessed. Transcriptomics analysis showed similar responses across all CNTs, with inflammation, cellular stress, metabolism, and DNA damage responses being affected. One pristine SWCNT was found to be the most potent and potentially fibrogenic, warranting further toxicity testing.
Article
Toxicology
Anne-Marie V. Fortin, Alexandra S. S. Long, Andrew Williams, Matthew J. J. Meier, Julie Cox, Claire Pinsonnault, Carole L. L. Yauk, Paul A. A. White
Summary: The conventional battery for genotoxicity testing is not suitable for assessing a large number of chemicals. New Approach Methodologies (NAMs) have been developed to accelerate hazard assessment and reduce reliance on time-consuming and resource-intensive in vivo tests. This study investigated the utility of integrating the TGx-DDI transcriptomic biomarker with MicroFlow(R) and MultiFlow(R) assays for screening data-poor compounds. The results show that this integrated approach is effective for genotoxicity assessment.
FRONTIERS IN TOXICOLOGY
(2023)
Article
Multidisciplinary Sciences
Marc A. Beal, Matthew J. Meier, Angela Dykes, Carole L. Yauk, Iain B. Lambert, Francesco Marchetti
Summary: This study provides a comprehensive and detailed map of amino acid residues affecting the structure and catalytic activity of the beta-gal enzyme, based on the analysis of lacZ mutations.
Article
Toxicology
Xiaotong Wang, Andrea Rowan-Carroll, Matthew J. Meier, Andrew Williams, Carole L. Yauk, Barbara F. Hales, Bernard Robaire
Summary: Despite the increasing number of studies on the potential risks associated with exposure to organophosphate esters (OPEs), their molecular mechanisms of action are still poorly understood. In this study, the effects of commonly detected OPEs on gene expression in human ovarian granulosa cells were investigated using the high-throughput TempO-Seq platform. The results revealed that OPEs had different effects on various biological pathways, with inhibition of the cholesterol biosynthetic pathway being the predominant effect at lower concentrations. At higher concentrations, OPEs primarily affected pathways related to cell cycle progression and stress responses.
TOXICOLOGICAL SCIENCES
(2023)