A5012904082- Carcinogens and Genotoxicity Assessment
- Eicosanoids and Hypertension Pharmacology
- Chemotherapy-induced cardiotoxicity and mitigation
- Nitric Oxide and Endothelin Effects
- CRISPR and Genetic Engineering
- Erythrocyte Function and Pathophysiology
- Asthma and respiratory diseases
- Sulfur Compounds in Biology
- 3D Printing in Biomedical Research
- Animal testing and alternatives
- Cystic Fibrosis Research Advances
- Advanced Chemical Sensor Technologies
- Molecular Biology Techniques and Applications
- Pancreatic function and diabetes
- Cancer Treatment and Pharmacology
- Neonatal Respiratory Health Research
- Blood groups and transfusion
- Effects and risks of endocrine disrupting chemicals
- Biopolymer Synthesis and Applications
- Fatty Acid Research and Health
- DNA Repair Mechanisms
- Computational Drug Discovery Methods
- Advanced Sensor and Energy Harvesting Materials
- Respiratory Support and Mechanisms
- Inflammatory mediators and NSAID effects
United States Food and Drug Administration
2010-2025
Center for Drug Evaluation and Research
2010-2025
University of Southern California
1990-1997
Rogers (United States)
1996
Children's Hospital of Los Angeles
1990-1993
University of California, Davis
1984-1991
Martinez VA Medical Center
1991
Human liver-derived metabolically competent HepaRG cells have been successfully employed in both two-dimensional (2D) and 3D spheroid formats for performing the comet assay micronucleus (MN) assay. In present study, we investigated expanding genotoxicity endpoints evaluated by detecting mutagenesis using two error-corrected next generation sequencing (ecNGS) technologies, Duplex Sequencing (DS) High-Fidelity (HiFi) Sequencing. Both 2D spheroids were exposed 72 h to N-nitrosodimethylamine...
Traditionally, only circulating concentrations of parent drug have been measured in the rodent and nonrodent test species used for safety assessments served as an index systemic exposure comparisons to human exposures. Circulating metabolites generally specialized circumstances (e.g., compound was extensively metabolized). Measurement is usually sufficient when metabolite profile humans similar that at least one animal nonclinical assessment. However, it possible formed might not be present...
Abstract The endogenous X‐linked PIG‐A gene is involved in the synthesis of glycosyl phosphatidyl inositol (GPI) anchors that tether specific protein markers to exterior mammalian cell cytoplasmic membranes. Earlier studies rodent models indicate Pig‐a mutant red blood cells (RBCs) can be induced animals treated with genotoxic agents, and flow cytometry used identify rare RBCs deficient GPI‐anchored protein, CD59, as a marker mutation. We investigated if similar approach could for detecting...
The organotypic human air-liquid-interface (ALI) airway tissue model has been used as an in vitro cell culture system for evaluating the toxicity of inhaled substances. ALI cultures are highly differentiated, which made it challenging to evaluate genetic toxicology endpoints. In current study, we assayed DNA damage with high-throughput CometChip assay and quantified mutagenesis Duplex Sequencing, error-corrected next-generation sequencing method capable detecting a single mutation per 107...
Tert-butylhydroquinone (TBHQ) is a monofunctional Phase II enzyme inducer, which produces reactive oxygen species. Incubation with sublethal concentration of TBHQ increased the activities both gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase (GCS), although mechanisms are different (Liu colleagues, accompanying manuscript). In this study, we found that intracellular glutathione (GSH) content in rat lung epithelial L2 cells. cells pretreated nontoxic (50 microM)...
Sublethal quinone-mediated oxidative stress stimulates increases in the activities and mRNA levels of gamma-glutamyl transpeptidase (GGT) gamma-glutamylcysteine synthetase (GCS) rat lung epithelial L2 cells [Kugelman, A. et al. 1994. Am. J. Respir. Cell Mol. Biol. 11:586-592; Shi, M. Chem. 269:26512-26517]. The present study demonstrated that quinone-induced these two enzymes were differentially regulated. exposed to various concentrations tertiary-butylhydroquinone (TBHQ) for different...
With the advent of new technologies (e.g., genomics, automated analyses, and in vivo monitoring), regulations reduction animal tests by European REACH), approaches to toxicology Toxicity Testing 21st Century, National Research Council), field regulatory genetic is undergoing a serious re-examination. Within this context, Toxicological Sciences has published series articles its Forum Section on theme, "Genetic Assessment: Employing Best Science for Human Safety Evaluation" (beginning with...
The micronucleus (MN) assay is a core test used to evaluate genotoxic potential of xenobiotics. traditional in vitro MN usually conducted cells lacking metabolic competency or by supplementing cultures with an exogenous rat S9 system, which creates significant limitation for detecting metabolites. Our previous study demonstrated that compared HepG2, HepaRG exhibited significantly higher level CYP450 enzyme activities and detected greater portion carcinogens requiring activation using the...
Three-dimensional (3D) culture systems are increasingly being used for genotoxicity studies due to improved cell-to-cell interactions and tissue-like structures that limited or lacking in 2D cultures. The present study optimized a 3D system using metabolically competent HepaRG cells vitro testing. spheroids, formed 96- 384-well ultra-low attachment plates, were exposed various concentrations of 34 test articles, including 8 direct-acting 11 indirect-acting genotoxicants/carcinogens as well...
Alveolar macrophages (AM) have been found to suffer significant functional deficits in response nitrogen dioxide (NO2) exposure. The present investigation examined changes the activation of AM arachidonate metabolism and superoxide production an environmentally relevant level NO2. Rats were exposed 0.5 ppm NO2 for periods 0.5–10 d obtained by bronchoalveolar lavage (BAL). exposure produced complex effects upon both unstimulated stimulated metabolism. Unstimulated synthesis leukotriene B4...
Abstract Background Cisplatin is a primary chemotherapy choice for various solid tumors. DNA damage caused by cisplatin results in apoptosis of tumor cells. Cisplatin‐induced damage, however, may also result mutations normal cells and the initiation secondary malignancies. In current study, we have used erythrocyte PIG‐A assay to evaluate mutagenesis non‐tumor hematopoietic tissue cancer patients receiving chemotherapy. Methods Twenty‐one head neck undergoing treatment with were monitored...