Robert H. Heflich

Comparative genotoxicity assessment of ortho-phthalaldehyde using human in vitro organotypic airway epithelial cultures and standard in vitro genotoxicity assays

Yuan Le, Yueyi Sun, Xilin Li, Rebecca A. Wynne et autres

us (code pays fourni par la source)

Adjusting the Preincubation Conditions to Enhance the Ames Test for Detecting the Mutagenicity of N ‐Nitrosamines

Michelle E. Bishop, Audrey M Sims, Sharon K Guerrero, Kamela Mitchell et autres

Conducting S9-mediated preincubations at slightly acid pHs (e.g., pH 5.0 to pH 6.5) has been reported to enhance the mutagenicity of small-molecule nitrosamines in the Ames test. In this study, we have evaluated the effect of adjusting the preincubation mix used in …

us (code pays fourni par la source)

Mutagenicity of N -nitroso-fluoxetine and N -nitroso-varenicline in human HepaRG cell models

J.H. Seo, Hannah S Xu, Javier R. Revollo, Jaime A. Miranda et autres

Nitrosamine drug substance-related impurities (NDSRIs) have raised significant concern among the pharmaceutical industry and regulatory agencies, prompting a need to establish methods to determine the mutagenic risks associated with these substances. As human, metabolically competent HepaRG cells previously showed promise in evaluating …

us, gb (code pays fourni par la source)

Nitrosamine Ames Data Review and Method Development: proceedings of a US FDA/HESI workshop

Aisar H. Atrakchi, Raechel Puglisi, Joel P. Bercu, Jennifer R. Cheung et autres

Detection of N-nitrosamines (NA) in pharmaceuticals became a point of interest due to the mutagenic and carcinogenic potential of some compounds of this class, and their identification as nitrosated forms of marketed drugs, otherwise known as NA Drug Substance-Related Impurities (NDSRIs). The …

us, fr, de, gb, ca, nl (code pays fourni par la source)

Mutagenicity of EAT-positive NDSRIs in HepaRG spheroids

J.H. Seo, Hannah Xu, Javier R. Revollo, Jaime A. Miranda et autres

The Enhanced Ames Test (EAT) is currently recommended by regulatory authorities for evaluating the mutagenicity of N -nitrosamine drug impurities, including nitrosamine drug substance-related impurities (NDSRIs). In previous studies, we developed protocols to evaluate the genotoxicity and mutagenicity of NDSRIs in both …

us (code pays fourni par la source)

Detection of In Vivo Mutation in the Hprt and Pig-a Genes of Rat Lymphocytes

Vasily N. Dobrovolsky, Joseph G. Shaddock, Roberta A. Mittelstaedt, Daishiro Miura et autres

us, jp (code pays fourni par la source)

Mutation accumulation following extended exposure of human HepaRG cells to a genotoxic carcinogen

Xiaoqing Guo, J.H. Seo, Jaime A. Miranda, Hannah Shibo Xu et autres

Accurately evaluating chemical risk may benefit from the development of human-relevant models capable of capturing the effects of treatments that closely mimic real-world environmental and pharmaceutical exposures. Building on our previous work (Seo et al. Arch Toxicol 98:1919-1935),Citation1 where cytotoxicity compromised mutation …

us (code pays fourni par la source)

Genotoxicity evaluation of ten nitrosamine drug substance-related impurities using 2D and 3D HepaRG cell models

Hannah Xu, Xilin Li, Aisar H. Atrakchi, Timothy J. McGovern et autres

us (code pays fourni par la source)

N-nitroso-ethylisopropylamine mutagenicity in rat liver using the cII transgenic mutation assay and duplex sequencing analysis of genomic DNA

Li Xia, Jian Yan, Ying Chen, Kamela Mitchell et autres

values for induced mutation indicate that DS analysis exhibited higher sensitivity than cII assay for detecting the mutations induced by NEIPA.

us (code pays fourni par la source)

Comparative DNA damage induced by eight nitrosamines in primary human and macaque hepatocytes

Ji‐Eun Seo, Xiaobo He, Matthew Bryant, Aisar H. Atrakchi et autres

us (code pays fourni par la source)

HESI GTTC ring trial: Concordance between Ames and rodent carcinogenicity outcomes for N-nitrosamines (NAs) with rat and hamster metabolic conditions

Joel P. Bercu, Alejandra Trejo‐Martin, Connie L. Chen, Maik Schuler et autres

A multi-sector study (i.e., Ring Trial) was designed to improve the in vitro detection of N -nitrosamine (NA)-associated mutagenicity by optimizing the bacterial reverse mutation (i.e., Ames) assay protocol and testing various conditions on the sensitivity and specificity for the prediction of …

us, gb, fr, de, ca, nl, ch, ie (code pays fourni par la source)

Integration of the rat liver micronucleus assay into a 28-day treatment protocol: testing the genotoxicity of 4 small-molecule nitrosamines with different carcinogenic potencies and tumor target specificities

Xiaoqing Guo, Ji‐Eun Seo, Hannah Xu, Jian Yan et autres

Several potent carcinogenic nitrosamines, including N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA), induce micronuclei in the micronucleated hepatocyte (MNHEP) assay but not in the micronucleated reticulocyte (MNRET) assay. However, the MNHEP assay is not as frequently used as the MNRET assay for evaluating in …

us (code pays fourni par la source)