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Cited by 49Cancer, Hypoxia, and MetabolismUltrasound and Hyperthermia ApplicationsCancer Cells and Metastasis

Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma

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Moen, Ingrid, Tronstad, Karl J, Kolmannskog, Odd, Salvesen, Gerd S, Reed, Rolf K, Stuhr, Linda EB·2009·BMC Cancer
DOI 10.1186/1471-2407-9-446PMC PMC2805681
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Abstract

Background: Hypoxia is associated with increased resistance to chemo- and radiation-therapy. Hyperoxic treatment (hyperbaric oxygen) has previously been shown to potentiate the effect of some forms of chemotherapy, and this has been ascribed to enhanced cytotoxicity or neovascularisation. The aim of this study was to elucidate whether hyperoxia also enhances any actual uptake of 5FU (5-fluorouracil) into the tumor tissue and if this can be explained by changes in the interstitium and extracellular matrix. Methods: One group of tumor bearing rats was exposed to repeated hyperbaric oxygen (HBO) treatment (2 bar, pO 2= 2 bar, 4 exposures à 90 min), whereas one group was exposed to one single identical HBO treatment. Animals housed under normal atmosphere (1 bar, pO 2= 0.2 bar) served as controls. Three doses of 5FU were tested for dose response. Uptake of [3 H]-5FU in the tumor was assessed, with special reference to factors that might have contributed, such as interstitial fluid pressure (P if), collagen content, oxygen stress (measured as malondialdehyd levels), lymphatics and transcapillary transport in the tumors. Results: The uptake of the cytostatic agent increases immediately after a single HBO treatment (more than 50%), but not 24 hours after the last repeated HBO treatment. Thus, the uptake is most likely related to the transient increase in oxygenation in the tumor tissue. Factors like tumor P if and collagen content, which decreased significantly in the tumor interstitium after repeated HBO treatment, was without effect on the drug uptake. Conclusion: We showed that hyperoxia increases the uptake of [3 H]-5FU in DMBA-induced mammary tumors per se, independently of changes in P if, oxygen stress, collagen fibril density, or transendothelial transport alone. The mechanism by which such an uptake occur is still not elucidated, but it is clearly stimulated by elevated pO 2.

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  • The cytotoxicity of first-line chemotherapeutics, such as cisplatin, carboplatin, DOX, paclitaxel, and 5-fluorouracil, is enhanced in the presence of hyperoxia.

    “The cytotoxicity of first‐line chemotherapeutics, such as cisplatin, carboplatin, DOX, paclitaxel, and 5‐fluorouracil, is enhanced in the presence of hyperoxia (Table 2). 383 , 389 , 399 , 400 , 401 , 402”

    From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [389]

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Authors
Moen, I., Tronstad, K. J., Kolmannskog, O., Salvesen, G. S., Reed, R. K., & Stuhr, L. E.
Affiliations
University of Bergen (NO)
Corresponding author
Stuhr, Linda EB
ORCID
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2009-12
Volume
9
Issue
1
Pages
446-446
ISSN
1471-2407 (ISSN-L)
DOI
10.1186/1471-2407-9-446
PMC
PMC2805681
OpenAlex
W2112514371
Cited by
49
References
52
Citations by year
2026: 1 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 8 · 2014: 3 · 2013: 2 · 2012: 6
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Kreftforeningen
  • Helse Vest
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
hyperbaric oxygen therapy, hyperoxia, 5-fluorouracil, drug uptake, mammary tumors, interstitial fluid pressure, tumor stroma, collagen, oxygen stress, malondialdehyde, transcapillary transport, lymphatic vessels, extracellular matrix, DMBA-induced tumors, tumor oxygenation, chemosensitization
MeSH terms
Adenocarcinoma, Animals, Antimetabolites, Antineoplastic, Blood Volume, Dose-Response Relationship, Drug, Female, Fluorouracil, Hyperbaric Oxygenation, Lymph, Mammary Neoplasms, Experimental, Osmotic Pressure, Stromal Cells, Rats, Sprague-Dawley, Reactive Oxygen Species, Hyperoxia, Extracellular Fluid, Rats

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