ArticleJournal of the American Chemical Society2007
DNA strand damage product analysis provides evidence that the tumor cell-specific cytotoxin tirapazamine produces hydroxyl radical and acts as a surrogate for O(2).
Article in Journal of the American Chemical Society, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Long-Patch Base Excision Repair of 5'-DNA-Peptide Cross-Links Derived from Abasic DNA Lesions.Biochemistry · 2026Article
- Supramolecular Aggregation-Induced Emission Photosensitizer Encapsulated by Cucurbit[8]uril Nanocavity Boosts Hypoxia-Activated Tumor Therapy.ACS applied nano materials · 2025Article
- Spin Trapping Hydroxyl and Aryl Radicals of One-Electron Reduced Anticancer Benzotriazine 1,4-Dioxides.Molecules (Basel, Switzerland) · 2022Article
- Good Steel Used in the Blade: Well-Tailored Type-I Photosensitizers with Aggregation-Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Benzotriazine Di-Oxide Prodrugs for Exploiting Hypoxia and Low Extracellular pH in Tumors.Molecules (Basel, Switzerland) · 2019Article
- Application of Suzuki-Miyaura and Buchwald-Hartwig Cross-coupling Reactions to the Preparation of Substituted 1,2,4-Benzotriazine 1-Oxides Related to the Antitumor Agent Tirapazamine.Journal of heterocyclic chemistry · 2017Article
- When DNA repair goes wrong: BER-generated DNA-protein crosslinks to oxidative lesions.DNA repair · 2016Review
- Quinoxaline 1,4-di-N-Oxides: Biological Activities and Mechanisms of Actions.Frontiers in pharmacology · 2016Review
- Enzyme mechanism-based, oxidative DNA-protein cross-links formed with DNA polymerase β in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Toward hypoxia-selective DNA-alkylating agents built by grafting nitrogen mustards onto the bioreductively activated, hypoxia-selective DNA-oxidizing agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine).The Journal of organic chemistry · 2014Article
- Reactive oxygen species (ROS) inducible DNA cross-linking agents and their effect on cancer cells and normal lymphocytes.Journal of medicinal chemistry · 2014Article
- Isotopic labeling experiments that elucidate the mechanism of DNA strand cleavage by the hypoxia-selective antitumor agent 1,2,4-benzotriazine 1,4-di-N-oxide.Chemical research in toxicology · 2014Article
- Article
- Synthesis, preferentially hypoxic apoptosis and anti-angiogenic activity of 1,2,4-benzotrazin-3-amine 1,4-dioxide bearing alkyl linkers with 1,2,4-benzotrazin-3-amine 1-oxide derivatives.Anti-cancer agents in medicinal chemistry · 2014Article
- Hypoxia-selective, enzymatic conversion of 6-nitroquinoline into a fluorescent helicene: pyrido[3,2-f]quinolino[6,5-c]cinnoline 3-oxide.The Journal of organic chemistry · 2012Article
- Targeting hypoxia in cancer therapy.Nature reviews. Cancer · 2011Review
- Synthesis, Crystal Structure, and Rotational Energy Profile of 3-Cyclopropyl-1,2,4-benzotriazine 1,4-Di-N-oxide.Journal of chemical crystallography · 2010Article
- DNA strand cleaving properties and hypoxia-selective cytotoxicity of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide.Bioorganic & medicinal chemistry · 2010Article
- An overview of chemical processes that damage cellular DNA: spontaneous hydrolysis, alkylation, and reactions with radicals.Chemical research in toxicology · 2009Review
- Tandem mass spectrometry-based detection of c4'-oxidized abasic sites at specific positions in DNA fragments.Chemical research in toxicology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The compound 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, TPZ) is a clinically promising anticancer agent that selectively kills the oxygen-poor (hypoxic) cells found in solid tumors. It has long been known that, under hypoxic conditions, TPZ causes DNA strand damage that is initiated by the abstraction of hydrogen atoms from the deoxyribose phosphate backbone of duplex DNA, but exact chemical mechanisms underlying this process remain unclear. Here we describe detailed characterization of sugar-derived products arising from TPZ-mediated strand damage. We find that the action of TPZ on duplex DNA under hypoxic conditions generates 5-methylene-2-furanone (6), oligonucleotide 3'-phosphoglycolates (7), malondialdehyde equivalents (8 or 9), and furfural (10). These results provide evidence that TPZ-mediated strand damage arises via hydrogen atom abstraction from both the most hindered (C1') and least hindered (C4' and C5') positions of the deoxyribose sugars in the double helix. The products observed are identical to those produced by hydroxyl radical. Additional experiments were conducted to better understand the chemical pathways by which TPZ generates the observed DNA-damage products. Consistent with previous work showing that TPZ can substitute for molecular oxygen in DNA damage reactions, it is found that, under anaerobic conditions, reaction of TPZ with a discrete, photogenerated C1'-radical in a DNA 2'-oligodeoxynucleotide cleanly generates the 2-deoxyribonolactone lesion (5) that serves as the precursor to 5-methylene-2-furanone (6). Overall, the results provide insight regarding the chemical structure of the DNA lesions that confront cellular repair, transcription, and replication machinery following exposure to TPZ and offer new information relevant to the chemical mechanisms underlying TPZ-mediated strand cleavage.
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What OpenQuestion holds
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.