Related Experiment Video
Updated: Sep 21, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
Published on: January 20, 2016
Cytochrome P-450 dependent binding of methapyrilene to DNA in vitro
1Department of Pharmacology, School of Medicine, University of California, Los Angeles 90024.
Abstract:
Methapyrilene ([14C]MPH) was found to bind to calf thymus DNA only after activation by both rat liver microsomes and NADPH. The cytochrome P-450 inhibitors 2,4-dichloro-6-phenylphenoxyethylamine, 2-diethylaminoethyl-2,2-diphenylvalerate and metyrapone inhibited binding, but methimazole, a flavin-dependent monooxygenase inhibitor, had no effect. However, 1,2-epoxy-3,3,3-trichloropropane, an epoxide hydrolase inhibitor, decreased binding by 30%. Pre-treatment of rats with isosafrole, pregnenolone-16 alpha-carbonitrile or phenobarbital had little or no effect on binding while 3-methylcholanthrene pretreatment decreased binding by 37%. Incubations in the presence of either N-acetylcysteine, glutathione, catalase or glutathione-peroxidase decreased binding to DNA while superoxide dismutase had no effect. These data suggest that MPH is metabolically activated to a species which binds to DNA and that this activation may be mediated by cytochrome P-450 isozymes.
More Related Videos
09:33Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
06:07Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Related Concept Videos
Phase II Reactions: Methylation Reactions
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Inhibitors of Bacterial DNA Synthesis