Methylphenidate hydrochloride (MPH), a widely prescribed pediatric drug for attention deficit hyperactivity disorder, induced liver adenocarcinomas in B6C3F1 mice exposed to 500 ppm in feed for 2 years (Dunnick and Hailey (1995) [14]). In order to determine if the induction of liver tumors was by a mutagenic mode of action, groups of male Big Blue (BB) mice (B6C3F1 background) were fed diets containing 50-4000 ppm MPH for 4, 12, or 24 weeks. At sacrifice, the livers were removed and the cII mutant frequency (MF) and spectrum of cII mutations were determined. In addition, the frequencies of micronucleated reticulocytes (MN-RETs) and normochromatic erythrocytes (MN-NCEs) were measured in peripheral blood erythrocytes as was the Hprt MF in splenic lymphocytes. Food consumption and body weight gain/loss were recorded weekly for each animal. The levels of MPH and RA were determined immediately before sacrifice in the serum of mice fed MPH for 24 weeks. A significant loss in body weights (p
Download full-text PDF
Source
http://dx.doi.org/10.1016/j.mrgentox.2009.09.004 DOI Listing Publication Analysis
Top Keywords
Similar Publications
Machine learning enhances genotoxicity assessment using MultiFlow® DNA damage assay.
Environ Mol Mutagen
December 2024
Research and Development, Preclinical Safety, Sanofi, Industriepark Hoechst, Frankfurt am Main, Germany.
Genotoxicity is a critical determinant for assessing the safety of pharmaceutical drugs, their metabolites, and impurities. Among genotoxicity tests, mechanistic assays such as the MultiFlow® DNA damage assay (MFA) allows the investigations on mode of action (MoA) of DNA damage through four mechanistic markers recorded at two time points. Previous studies have shown that machine learning (ML) can enhance precision on classifying the MoA of genotoxicants.
View Article and Find Full Text PDFChromatographic Separation and Quantification of Nine Nitrosamine Genotoxic Impurities in a Single Method in Nebivolol Tablet by Using Validated Ultra-Sensitive Liquid Chromatography: Mass Spectrometry Analytical Method.
J Chromatogr Sci
January 2025
Analytical Research Laboratory, Cadila Pharmaceuticals Ltd., Dholka, Ahmedabad 382225, India.
N-nitrosamine impurities have been detected in a vast variety of drug substances and drug products, showing concern for regulatory aspects. To meet the regulatory requirement for the concerned impurity, a sensitive analytical method capable of quantifying these impurities at a lower level with accuracy and precision is required. This article focuses on the development and validation of an analytical method for the simultaneous detection of nine nitrosamine impurities in a single method for nebivolol drug product using liquid chromatography-mass spectrometry/mass spectrometry-atmospheric pressure chemical ionization (LC-MS/MS-APCI).
View Article and Find Full Text PDFTwo-dimensional liquid chromatography based on different modulations for the determination of Aristolochic Acid Ⅰ in Asari Radix et Rhizoma.
J Chromatogr A
January 2025
Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China. Electronic address:
Asari Radix et Rhizoma (ARR) is a traditional Chinese herbal medicine derived from the genus Asarum in the Aristolochiaceae family, which has been widely used for years. Aristolochic acids in it significantly restrict the clinical application of ARR due to its nephrotoxic and carcinogenic properties, of which aristolochic acid I (AA I) is the most representative. The present paper describes two 2D-LC systems modulated by a sample loop and a trap column respectively for the detection of trace aristolochic acid I in ARR.
View Article and Find Full Text PDFSystematic Characterisation of the Fragmentation of Flavonoids Using High-Resolution Accurate Mass Electrospray Tandem Mass Spectrometry.
Molecules
November 2024
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
Flavonoids are a class of polyphenolic secondary metabolites found in plants. Due to their ubiquity in our daily dietary intake and their major anti-oxidative, anti-inflammatory and anti-mutagenic activities, they have been a major focus of wide-ranging research for the past two decades. Mass spectrometry combined with liquid chromatography is one of the most popular techniques for the analysis of flavonoids.
View Article and Find Full Text PDFInvestigation of mutagenicity of styrene in tumor target and non-target tissues of transgenic Big Blue® mice.
Environ Mol Mutagen
November 2024
General and Genetic Toxicology, Charles River Laboratories, Ashland, Ohio, USA.
Article Synopsis
- - A study investigated if styrene, known to cause lung tumors in mice but not in rats, contributes to genotoxicity as a potential first step in tumor development.
- - Transgenic mice were treated with varying doses of styrene for 28 days, and the frequency of mutations in lung and non-lung tissues was measured.
- - Results showed no increase in mutations in treated mice, indicating that styrene is unlikely to act as a mutagen in vivo and does not initiate lung tumors in this model.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!