Article
Toxicology
Ji-Eun Seo, Xilin Li, Yuan Le, Nan Mei, Tong Zhou, Xiaoqing Guo
Summary: This study compared the performance of HepaRG cells grown in 2D and 3D cultures in the high-throughput flow cytometry-based micronucleus (MN) assay. The results showed that 3D HepaRG spheroids exhibited higher sensitivity in detecting genotoxicants requiring metabolic activation. Integration of the MN and comet assays improved the sensitivity for detecting such genotoxicants, suggesting that HepaRG spheroids may contribute to New Approach Methodologies for genotoxicity assessment.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Tereza Cervena, Andrea Rossnerova, Tana Zavodna, Jitka Sikorova, Kristyna Vrbova, Alena Milcova, Jan Topinka, Pavel Rossner
Summary: The evaluation of genotoxicity induced by nanomaterials in bronchial epithelial cells using different variants of the micronuclei assay showed that the DNA damage level is affected by the selected methodological approach. Transmission electron microscopy demonstrated the impact of cytochalasin-B on the transportation of NMs into cells, while dynamic light scattering measurement revealed the behavior of NMs in culture media. The genotoxic potential of various TiO2 and Ag particles differed, with the application of cytochalasin-B tending to increase the percentage of aberrant cells.
Article
Clinical Neurology
Elia Sechi, Marina Buciuc, Sean J. Pittock, John J. Chen, James P. Fryer, Sarah M. Jenkins, Adrian Budhram, Brian G. Weinshenker, A. Sebastian Lopez-Chiriboga, Jan-Mendelt Tillema, Andrew McKeon, John R. Mills, W. Oliver Tobin, Eoin P. Flanagan
Summary: This study investigated the positive predictive value of myelin oligodendrocyte glycoprotein (MOG)-IgG1 testing in a single tertiary referral center, revealing a PPV of 72% with variations depending on antibody titer and clinical phenotypes at testing.
Article
Engineering, Environmental
Mauricius Marques dos Santos, Camille Cheriaux, Shenglan Jia, Mikael Thomas, Herve Gallard, Jean-Philippe Croue, Pascal Carato, Shane Allen Snyder
Summary: This study reveals that 1,3-diphenylguanidine (DPG) and its chlorinated by-products exhibit significant toxicity and genotoxicity, affecting cell bioenergetic processes and mitochondrial function.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Engineering, Environmental
Agathe Bourchy, Sarah A. Saslow, Benjamin D. Williams, Nancy M. Avalos, Wooyong Um, Nathan L. Canfield, Lucas Sweet, Gary L. Smith, R. Matthew Asmussen
Summary: This study focuses on the behavior of technetium-99 (Tc) in a hydrated-lime based waste form. The results show that the hydrated-lime formulation demonstrates improved Tc retention compared to a fly ash-based formulation, with sustained performance over time.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Environmental Sciences
Yax Thakkar, Holger Moustakas, Nynke Moelijker, Giel Hendriks, Inger Brandsma, Stefan Pfuhler, Anne Marie Api
Summary: The utility of the ToxTracker assay in animal alternative testing strategies was evaluated by testing the genotoxic potential of four fragrance materials. These materials had previously been evaluated using in vitro and in vivo micronucleus assays. In addition, reconstructed human skin micronucleus studies were conducted. While the in vitro micronucleus assays showed positive results, both in vivo and 3D skin micronucleus assays showed negative results. The ToxTracker assay, combined with in silico predictions, was able to identify mechanisms for the misleading positive outcomes observed in the in vitro micronucleus assays.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(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
Gastroenterology & Hepatology
Jordan K. Voss, Derek W. Ebner, Keli N. Burger, Douglas W. Mahoney, Mary E. Devens, Kari L. Lowrie, John B. Kisiel
Summary: Multitarget stool DNA (mt-sDNA) testing is an effective screening method for colorectal cancer. The positive rate and positive predictive value (PPV) of mt-sDNA were examined in a second round of testing and found to be similar to those in the first round. These findings confirm the usefulness of mt-sDNA for CRC screening.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Oncology
Habib Ghaznavi, Mohammad Reza Hajinezhad, Milad Shirvaliloo, Sheida Shahraki, Kourosh Shahraki, Ramin Saravani, Sakine Shirvalilou, Omolbanin Shahraki, Ziba Nazarlou, Roghayeh Sheervalilou, Saman Sargazi
Summary: The aim of this study was to evaluate the cytotoxicity, genotoxicity, and histopathological effects of Fe2O3@Au-FA NPs using in vitro and in vivo models. The results showed no significant toxicity of the nanoparticles at the safe dose in both in vitro and in vivo experiments. These findings suggest that Fe2O3@Au-FA NPs could be potential candidates in the field of nanobiomedicine at appropriate doses.
Article
Food Science & Technology
Bara Krizkovska, Martin Schatz, Jan Lipov, Jitka Viktorova, Eva Jablonska
Summary: This article presents a new method for measuring in vitro genotoxicity using the phosphorylated histone biomarker (gamma H2AX). The authors used flow cytometry and microscopy to detect the gamma H2AX response and performed bioimage analysis using the open-source software ImageJ. They provided workflows, data, and scripts for further improvement of bioimage analysis methods.
Article
Biochemistry & Molecular Biology
Nan Guo, Meiying Cai, Min Lin, Huili Xue, Hailong Huang, Liangpu Xu
Summary: Early and intermediate serological screening cannot detect sex chromosome abnormalities. Noninvasive prenatal testing (NIPT) is the only available procedure for screening such disorders. This study found that karyotype analysis and SNP array can improve the diagnostic accuracy for pregnant women with a positive NIPT result indicating sex chromosome abnormalities. The study also identified age-related differences in the positive predictive value.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Multidisciplinary Sciences
Faisal S. Minhaj, Sarah C. Bonaparte, Cassandra Boutelle, Ryan M. Wallace
Summary: Historical targets for country-level animal rabies testing volumes were abandoned due to ethical and welfare concerns, and interpretation challenges of testing healthy animals. To-date, no quantitative threshold has been established for evaluating adequate surveillance capacity specific to suspected rabid animals. The purpose here is to establish quantitative testing thresholds for rabies suspected animals to assess a country's rabies surveillance capacity.
SCIENTIFIC REPORTS
(2023)
Article
Veterinary Sciences
Adrian J. Smith
Summary: There are good reasons to limit the use of animals in research and testing, ensure humane treatment, and provide reliable data. However, there is room for improvement in these areas. The Norecopa website offers resources to address these issues and promote better science, animal welfare, and safety.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Engineering, Chemical
Qinglin Su, Paul Hermant, Federica Casati, Bhakti Halkude, Wei Wu, Anjana Ramnath, Atul Dubey, Stephen Born, Bayan Takizawa, Salvatore Mascia
Summary: A predictive mathematical model was developed and implemented in a continuous manufacturing pilot plant for tablet dissolution. The model included the mass balance of API solute and the dissolution, diffusion, and population balance of API particles in the swollen tablet. Equivalence was demonstrated through comparison with experimental data, with all sampled tablets showing a similarity factor f(2) > 50. Concluding remarks and industrial perspectives on model predictive in vitro dissolution testing are provided.
Article
Virology
Michael J. Wilson, Dominic Sparkes, Chloe Myers, Anna A. Smielewska, Mir Mubariz Husain, Christopher Smith, Kathryn J. Rolfe, Hongyi Zhang, Hamid Jalal
Summary: Confirmatory testing is necessary to reduce false positives, but can lead to delays in results. Establishing a threshold for confirmatory testing can streamline the process and improve accuracy when needed.
JOURNAL OF CLINICAL VIROLOGY
(2021)
Article
Toxicology
Rita Roque Bravo, Helena Carmo, Joao Pedro Silva, Maria Joao Valente, Felix Carvalho, Maria de Lourdes Bastos, Diana Dias da Silva
ARCHIVES OF TOXICOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Benjamin Kopp, Ludovic Le Hegarat, Marc Audebert
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
(2020)
Article
Pharmacology & Pharmacy
Nelly Gueniche, Arnaud Bruyere, Melanie Ringeval, Elodie Jouan, Antoine Huguet, Ludovic Le Hegarat, Olivier Fardel
Article
Multidisciplinary Sciences
Pavlina Simeckova, Frantisek Hubatka, Jan Kotoucek, Pavlina Turanek Knotigova, Josef Masek, Josef Slavik, Ondrej Kovac, Jiri Neca, Pavel Kulich, Dominik Hrebik, Jana Straska, Katerina Pencikova, Jirina Prochazkova, Pavel Divis, Stuart Macaulay, Robert Mikulik, Milan Raska, Miroslav Machala, Jaroslav Turanek
SCIENTIFIC REPORTS
(2020)
Article
Cell Biology
Joanna Brzeszczynska, Filip Brzeszczynski, Kay Samuel, Katie Morgan, Steven D. Morley, John N. Plevris, Peter C. Hayes
Article
Genetics & Heredity
Benjamin Kopp, Pascal Sanders, Imourana Alassane-Kpembi, Valerie Fessard, Daniel Zalko, Ludovic Le Hegarat, Marc Audebert
Article
Pharmacology & Pharmacy
Nelly Gueniche, Antoine Huguet, Arnaud Bruyere, Denis Habauzit, Ludovic Le Hegarat, Olivier Fardel
Summary: This study evaluated the performance of six freely accessible Web-tools in predicting P-gp-mediated transport using a test set of 231 marketed drugs approved by the FDA from 2010 to 2020. The results showed that the predictions of P-gp substrate status by these online in silico methods may not meet the criteria commonly required for acceptable prediction, whether used alone or in combination. Therefore, caution should be exercised when considering predictions made by these tools.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2021)
Article
Toxicology
Audrey Barranger, Ludovic Le Hegarat
Summary: Toxicology is undergoing a significant shift from animal experimentation to animal-free methods for toxicity testing. The development of high-throughput DNA damage detection platforms using 3D cell models is urgently needed to improve in vitro genotoxicity assessment of chemical compounds. Hepatic cell lines serve as relevant models for studying liver functions. This study evaluated the performance of the high-throughput in vitro CometChip assay on 2D and 3D HepaRG cells and provides insights into the specific responses of these models.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Chemistry, Medicinal
Zeineb Marzougui, Sylvie Huet, Anne-Louise Blier, Ludovic Le Hegarat, Haifa Tounsi-Kettiti, Riadh Kharrat, Riadh Marrouchi, Valerie Fessard
Summary: In this study, the in vivo genotoxic effects of C17-sphinganine analog mycotoxin (C17-SAMT) were evaluated using comet assays and micronucleus assay. The results showed that C17-SAMT induced DNA damage in the duodenum and spleen, but had no significant effect on chromosome and genome damage in the bone marrow. Microscopic observations of the liver revealed increased mitosis and hepatocytes' cytoplasm clarification.
Article
Engineering, Environmental
Thibaut Leger, Patrick Balaguer, Ludovic Le Hegarat, Valerie Fessard
Summary: A study investigated the biological effects of the pesticide tebufenpyrad on liver cells using proteomics and metabolomics. The results showed an increase in metabolites and synthesis of mitochondrion constituents, fatty acid oxidation, and cellular uptake of lipids. The study also observed secretion of proteasome and inhibition of acute inflammation. The study concluded that the interaction of tebufenpyrad with the PPAR gamma transcription factor mediated the liver cell response.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Biochemical Research Methods
Andrew Collins, Peter Moller, Goran Gajski, Sona Vodenkova, Abdulhadi Abdulwahed, Diana Anderson, Ezgi Eyluel Bankoglu, Stefano Bonassi, Elisa Boutet-Robinet, Gunnar Brunborg, Christy Chao, Marcus S. S. Cooke, Carla Costa, Solange Costa, Alok Dhawan, Joaquin de Lapuente, Cristian Del Bo, Julien Dubus, Maria Dusinska, Susan J. J. Duthie, Naouale El Yamani, Bevin Engelward, Isabel Gaivao, Lisa Giovannelli, Roger Godschalk, Sofia Guilherme, Kristine B. B. Gutzkow, Khaled Habas, Alba Hernandez, Oscar Herrero, Marina Isidori, Awadhesh N. N. Jha, Siegfried Knasmueller, Ingeborg M. M. Kooter, Gudrun Koppen, Marcin Kruszewski, Carina Ladeira, Blanca Laffon, Marcelo Larramendy, Ludovic Le Hegarat, Angelique Lewies, Anna Lewinska, Guillermo E. E. Liwszyc, Adela Lopez de Cerain, Mugimane Manjanatha, Ricard Marcos, Mirta Milic, Vanessa Moraes de Andrade, Massimo Moretti, Damian Muruzabal, Matjaz Novak, Rui Oliveira, Ann-Karin Olsen, Norah Owiti, Mario Pacheco, Alok K. K. Pandey, Stefan Pfuhler, Bertrand Pourrut, Kerstin Reisinger, Emilio Rojas, Elise Runden-Pran, Julen Sanz-Serrano, Sergey Shaposhnikov, Ville Sipinen, Karen Smeets, Helga Stopper, Joao Paulo Teixeira, Vanessa Valdiglesias, Mahara Valverde, Frederique van Acker, Frederik-Jan van Schooten, Marie Vasquez, Johannes F. F. Wentzel, Maciej Wnuk, Annelies Wouters, Bojana Zegura, Tomas Zikmund, Sabine A. S. Langie, Amaya Azqueta
Summary: The comet assay is a versatile method for detecting various types of DNA damage in individual eukaryotic cells. It has been widely used in research, industry, and regulatory agencies, and has been adopted as an in vivo test for genotoxicity. The present document provides consensus protocols for applying the comet assay to different cell types, species, and types of DNA damage.
Article
Environmental Sciences
Adeline Clerge, Jeremie Le Goff, Emilie Brotin, Edwige Abeillard, Isabelle Vaudorne, Christophe Denoyelle, Ludovic Le Hegarat, Raphael Delepee
Summary: This study conducted a prospective study on seven oxy-PAHs to investigate their mutagenicity, genotoxicity, and cytotoxicity potentials. The results showed that oxy-PAHs can cause DNA damage and have potential carcinogenic risks in exposed populations. In vitro assays, including the Ames test, were used to evaluate the genotoxic and mutagenic effects of oxy-PAHs.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2023)
Article
Biochemistry & Molecular Biology
Zeineb Marzougui, Ludovic Le Hegarat, Kevin Hogeveen, Sylvie Huet, Riadh Kharrat, Riadh Marrouchi, Valerie Fessard
Summary: This study investigated the genotoxicity and cytotoxicity of C17-sphinganine analog mycotoxin (C17-SAMT) through in vitro assays. The results showed that C17-SAMT induced an increase in micronucleus formation in human lymphoblastoid TK6 cells and mitochondrial dysfunction in HepaRG cells. Further research is needed to fully understand the mode of action of this toxin. The study highlights the potential toxicity of C17-SAMT and emphasizes the importance of further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Toxicology
Marc Audebert, Ann-Sophie Assmann, Amaya Azqueta, Pavel Babica, Emilio Benfenati, Sylvie Bortoli, Peter Bouwman, Albert Braeuning, Tanja Burgdorf, Xavier Coumoul, Kloe Debizet, Maria Dusinska, Norman Ertych, Joerg Fahrer, Verena Fetz, Ludovic Le Hegarat, Adela Lopez de Cerain, Harm J. Heusinkveld, Kevin Hogeveen, Miriam N. Jacobs, Mirjam Luijten, Giuseppa Raitano, Cynthia Recoules, Elise Runden-Pran, Mariam Saleh, Iva Sovadinova, Martina Stampar, Lea Thibol, Celine Tomkiewicz, Ariane Vettorazzi, Bob van de Water, Naouale El Yamani, Bojana Zegura, Michael Oelgeschlaeger
Summary: Carcinogenic chemicals can be classified as genotoxic or non-genotoxic carcinogens. Genotoxic compounds cause DNA damage and can be detected through genotoxicity assays, while non-genotoxic compounds have diverse modes of action and do not have specific assays for detection. Evaluation of the carcinogenic potential of non-genotoxic compounds still relies on long-term studies in rodents, which are time-consuming, costly, and limited in their predictivity for human risk assessment. Therefore, there is an urgent need for new approach methodologies that integrate human-relevant in vitro assays and in silico tools to improve hazard assessment and risk assessment for chemical carcinogens.
FRONTIERS IN TOXICOLOGY
(2023)
Review
Environmental Sciences
Carol Beevers, Yoshifumi Uno, Krista Meurer, Shuichi Hamada, Kiyohiro Hashimoto, David Kirkland, Matthew J. Lebaron, Frank Le Curieux, Ludovic Le Hegarat, Hans-Joerg Martus, Kenichi Masumura, Wakako Ohyama, Daniel J. Roberts, Marie Vasquez, James Whitwell, Kristine L. Witt
Summary: The in vivo working group reached agreements on several issues, including the maximum doses for negative erythrocyte micronucleus tests, the validation of micronucleus assays in non-hematopoietic tissues, and nuisance factors in the comet assay. They found that the liver micronucleus test using six-week-old rats is sufficiently validated, but more research is needed to assess the impact of animal age. While current validation data are insufficient for an OECD test guideline, the methodologies can be considered as an appendix to OECD TG474.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2023)