ArticleOncotarget2016
Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 89 citations in OpenAlex.
- 5-Aminolevulinic Acid-Based Radiodynamic Therapy for Malignant Gliomas: A Conceptual Framework for Mitochondria-Centered Mechanisms, Target Cell States and Translational Perspectives.Life (Basel, Switzerland) · 2026Review
- Interferon regulatory factors: the next prospective targets for tissue ischemia-reperfusion injury?Frontiers in immunology · 2026Review
- Radiodynamic Therapy for High-Grade Glioma in Normoxic and Hypoxic Environments for High-Grade Glioma.Cancers · 2025Article
- Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy.Discover oncology · 2025Review
- Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy.Communications chemistry · 2024Review
- TAB182 regulates glycolytic metabolism by controlling LDHA transcription to impact tumor radiosensitivity.Cell death & disease · 2024Article
- A Review: Multi-Omics Approach to Studying the Association between Ionizing Radiation Effects on Biological Aging.Biology · 2024Review
- Graphene-Based Photodynamic Therapy and Overcoming Cancer Resistance Mechanisms: A Comprehensive Review.International journal of nanomedicine · 2024Review
- Profound DNA methylomic differences between single- and multi-fraction alpha irradiations of lung fibroblasts.Clinical epigenetics · 2023Article
- The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.Biomolecules · 2023Review
- Mitochondria Need Their Sleep: Redox, Bioenergetics, and Temperature Regulation of Circadian Rhythms and the Role of Cysteine-Mediated Redox Signaling, Uncoupling Proteins, and Substrate Cycles.Antioxidants (Basel, Switzerland) · 2023Article
- Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status.Cell reports. Medicine · 2023Article
- Article
- Unraveling Mitochondrial Determinants of Tumor Response to Radiation Therapy.International journal of molecular sciences · 2022Review
- Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus.International journal of molecular sciences · 2022Article
- Ion Transport and Radioresistance.Reviews of physiology, biochemistry and pharmacology · 2022Review
- The measurement and modification of hypoxia in colorectal cancer: overlooked but not forgotten.Gastroenterology report · 2022Review
- Mitochondrial superoxide dismutase overexpression and low oxygen conditioning hormesis improve the performance of irradiated sterile males.Scientific reports · 2021Article
- Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1.Cancer research and treatment · 2021Article
- Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression.International journal of molecular sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may explain difficulty in eliminating hypoxic tumor cells, a major cause of regrowth after therapy. Our analysis utilizes the Howard-Flanders and Alper formula, which describes the relationship of radiosensitivity with oxygen tension. Here, we assign and qualitatively assess the relative contributions of two important mechanisms. The first mechanism involves the emission of reactive oxygen species from the mitochondrial electron transport chain, which increases with oxygen tension. The second mechanism is related to an energy and repair deficit, which increases with hypoxia. Following a radiation exposure, the uncoupling of the oxidative phosphorylation system (proton leak) in mitochondria lowers the emission of reactive oxygen species which has implications for fractionated radiotherapy, particularly of hypoxic tumors. Our analysis shows that, in oxygenated tumor and normal cells, mitochondria, rather than the nucleus, are the primary loci of radiotherapy effects, especially for low linear energy transfer radiation. Therefore, the oxygen effect can be explained by radiation-induced effects in mitochondria that generate reactive oxygen species, which in turn indirectly target nuclear DNA.
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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.