ArticleChemical research in toxicology2017
DNA Adduct Profiles Predict in Vitro Cell Viability after Treatment with the Experimental Anticancer Prodrug PR104A.
Article in Chemical research in toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Tumor-Selective and Chemical Activation Strategies for Nitrogen Mustard Prodrugs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Multi-adductomics: Advancing mass spectrometry techniques for comprehensive exposome characterization.Trends in analytical chemistry : TRAC · 2024Article
- Liquid Chromatography-Mass Spectrometry Screening of Cyclophosphamide DNA Damage In Vitro and in Patients Undergoing Chemotherapy Treatment.Chemical research in toxicology · 2023Article
- Characterization and quantitation of busulfan DNA adducts in the blood of patients receiving busulfan therapy.Molecular therapy oncolytics · 2023Article
- Applications of Adductomics in Chemically Induced Adverse Outcomes and Major Emphasis on DNA Adductomics: A Pathbreaking Tool in Biomedical Research.International journal of molecular sciences · 2021Review
- Applying Tobacco, Environmental, and Dietary-Related Biomarkers to Understand Cancer Etiology and Evaluate Prevention Strategies.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- DNA Crosslinkomics: A Tool for the Comprehensive Assessment of Interstrand Crosslinks Using High Resolution Mass Spectrometry.Analytical chemistry · 2019Article
- Emerging Technologies in Mass Spectrometry-Based DNA Adductomics.High-throughput · 2019Review
- Urinary DNA adductomics - A novel approach for exposomics.Environment international · 2018Article
- Review
- The Future of DNA Adductomic Analysis.International journal of molecular sciences · 2017Article
- DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine.Chemical research in toxicology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
PR104A is an experimental DNA-alkylating hypoxia-activated prodrug that can also be activated in an oxygen-independent manner by the two-electron aldo-keto reductase 1C3. Nitroreduction leads to the formation of cytotoxic hydroxylamine (PR104H) and amine (PR104M) metabolites, which induce DNA mono and cross-linked adducts in cells. PR104A-derived DNA adducts can be utilized as drug-specific biomarkers of efficacy and as a mechanistic tool to elucidate the cellular and molecular effects of PR104A. Toward this goal, a mass spectrometric bioanalysis approach based on a stable isotope-labeled adduct mixture (SILAM) and selected reaction monitoring (SRM) data acquisition for relative quantitation of PR104A-derived DNA adducts in cells was developed. Use of this SILAM-based approach supported simultaneous relative quantitation of 33 PR104A-derived DNA adducts in the same sample, which allowed testing of the hypothesis that the enhanced cytotoxicity, observed by preconditioning cells with the transcription-activating isothiocyanate sulforaphane, is induced by an increased level of DNA adducts induced by PR104H and PR104M, but not PR104A. By applying the new SILAM-SRM approach, we found a 2.4-fold increase in the level of DNA adducts induced by PR104H and PR104M in HT-29 cells preconditioned with sulforaphane and a corresponding 2.6-fold increase in cytotoxicity. These results suggest that DNA adduct levels correlate with drug potency and underly the possibility of monitoring PR104A-derived DNA adducts as biomarkers of efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.