The impact of p53 function on the metabolic activation of the carcinogenic air pollutant 3-nitrobenzanthrone and its metabolites 3-aminobenzanthrone and N-hydroxy-3-aminobenzanthrone in human cells [PDF]
The tumour suppressor p53, encoded by TP53, is a key player in a wide network of signalling pathways. We investigated its role in the bioactivation of the environmental carcinogen 3-nitrobenzanthrone (3-NBA)found in diesel exhaust and its metabolites 3 ...
Arlt, Volker M +5 more
core +2 more sources
Whole Genome Sequencing of the Mutamouse Model Reveals Strain- and Colony-Level Variation, and Genomic Features of the Transgene Integration Site [PDF]
AbstractThe MutaMouse transgenic rodent model is widely used for assessing in vivo mutagenicity. Here, we report the characterization of MutaMouse’s whole genome sequence and its genetic variants compared to the C57BL/6 reference genome. High coverage (>50X) next-generation sequencing (NGS) of whole genomes from multiple MutaMouse animals from the ...
Matthew J. Meier +4 more
openaire +2 more sources
Abstract Exposure levels without appreciable human health risk may be determined by dividing a point of departure on a dose–response curve (e.g., benchmark dose) by a composite adjustment factor (AF). An “effect severity” AF (ESAF) is employed in some regulatory contexts.
Barbara L. Parsons +17 more
wiley +1 more source
Role of human aldo-keto reductases in the metabolic activation of the carcinogenic air pollutant 3-nitrobenzanthrone [PDF]
3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen detected in diesel exhaust particulate and ambient air pollution. It requires metabolic activation via nitroreduction to promote DNA adduct formation and tumorigenesis.
Albrecht Seidel +17 more
core +2 more sources
The development and prevalidation of anin vitromutagenicity assay based on MutaMouse primary hepatocytes, Part II: Assay performance for the identification of mutagenic chemicals [PDF]
As demonstrated in Part I, cultured MutaMouse primary hepatocytes (PHs) are suitable cells for use in anin vitrogene mutation assay due to their metabolic competence, their “normal” phenotype, and the presence of the MutaMouse transgene for reliable mutation scoring.
Cox, JA +3 more
openaire +4 more sources
Transferability and Reproducibility of the HepaRG CometChip Assay
ABSTRACT This interlaboratory evaluation of HepaRG CometChip was conducted to assess transferability and reproducibility of this new approach methodology (NAM) across four laboratories. Concentrations inducing up to ~70% relative cytotoxicity were determined by the organizing laboratory, and frozen chemical formulation blocks were sent to each ...
Leslie Recio +10 more
wiley +1 more source
BACKGROUND: Chemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer.
Berenbaum MC +7 more
core +2 more sources
Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their revaluation [PDF]
The threshold of toxicological concern (TTC) approach is a resource-effective de minimismethod for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies.
Abigail Jacobs +22 more
core +2 more sources
Transferability, Reproducibility and Sensitivity of Mutation Quantification by Duplex Sequencing
ABSTRACT Duplex Sequencing (DS) is an ultra‐accurate, error‐corrected next generation sequencing (ecNGS) technology for mutation analysis. A working group (WG) within Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee is investigating the suitability of ecNGS for regulatory mutagenicity testing, using DS as a model ...
Shaofei Zhang +23 more
wiley +1 more source
Cytochrome b5 impacts on cytochrome P450-mediated metabolism of benzo[a]pyrene and its DNA adduct formation:studies in hepatic cytochrome b5 /P450 reductase null (HBRN) mice [PDF]
Benzo[a]pyrene (BaP) is an environmental pollutant that, based on evidence largely from in vitro studies, exerts its genotoxic effects after metabolic activation by cytochrome P450s.
Arlt, Volker M. +11 more
core +4 more sources

