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

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dc.contributor.author Moen, Ingrid eng
dc.contributor.author Tronstad, Karl Johan eng
dc.contributor.author Kolmannskog, Odd eng
dc.contributor.author Salvesen, Gerd Signe eng
dc.contributor.author Reed, Rolf K. eng
dc.contributor.author Stuhr, Linda Elin Birkhaug eng
dc.date.accessioned 2011-08-23T09:21:47Z
dc.date.available 2011-08-23T09:21:47Z
dc.date.issued 2009-12-17 eng
dc.identifier.citation BMC Cancer 9(446) en_US
dc.identifier.issn 1471-2407 eng
dc.identifier.uri http://hdl.handle.net/1956/4891
dc.description.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, pO2 = 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, pO2 = 0.2 bar) served as controls. Three doses of 5FU were tested for dose response. Uptake of [³H]-5FU in the tumor was assessed, with special reference to factors that might have contributed, such as interstitial fluid pressure (Pif), 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 Pif 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 [³H]-5FU in DMBA-induced mammary tumors per se, independently of changes in Pif, 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 pO2. en_US
dc.language.iso eng eng
dc.publisher BioMed Central eng
dc.rights Attribution CC BY eng
dc.rights.uri http://creativecommons.org/licenses/by/2.0 eng
dc.title Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma eng
dc.type Journal article eng
dc.type Peer reviewed eng
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 eng
dc.rights.holder Copyright 2009 Moen et al; licensee BioMed Central
dc.type.version publishedVersion eng
bora.peerreviewed Peer reviewed eng
bibo.doi http://dx.doi.org/10.1186/1471-2407-9-446 eng
dc.identifier.doi http://dx.doi.org/10.1186/1471-2407-9-446


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