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Redox generation of nitric oxide to radiosensitize hypoxic cells

Mitchell, James B., DeGraff, William, Kim, Sungmee, Cook, John A., Gamson, Janet, Christodoulou, Danae, Feelisch, Martin and Wink, David A. (1998) Redox generation of nitric oxide to radiosensitize hypoxic cells International Journal of Radiation: Oncology, Biology, Physics, 42, (4), pp. 795-798. (doi:10.1016/S0360-3016(98)00327-7). (PMID:9845098).

Record type: Article


Purpose: Previous studies have shown that nitric oxide (NO) delivered from NO donor agents sensitizes hypoxic cells to ionizing radiation. In the present study, nitroxyl (NO?), a potential precursor to endogenous NO production, was evaluated for hypoxic cell radiosensitization, either alone or in combination with electron acceptor agents.

Methods and Materials: Radiation survival curves of Chinese hamster V79 lung fibroblasts under aerobic and hypoxic conditions were assessed by clonogenic assay. Hypoxia induction was achieved by metabolism-mediated oxygen depletion in dense cell suspensions. Cells were treated with NO? produced from the nitroxyl donor Angeli’s salt (AS, Na2N2O3, sodium trioxodinitrate), in the absence or presence of electron acceptor agents, ferricyanide, or tempol. NO concentrations resulting from the combination of AS and ferricyanide or tempol were measured under hypoxic conditions using an NO-sensitive electrode.

Results: Treatment of V79 cells under hypoxic conditions with AS alone did not result in radiosensitization; however, the combination of AS with ferricyanide or tempol resulted in significant hypoxic radiosensitization with SERs of 2.5 and 2.1, respectively. Neither AS alone nor AS in combination with ferricyanide or tempol influenced aerobic radiosensitivity. The presence of NO generated under hypoxic conditions from the combination of AS with ferricyanide or tempol was confirmed using an NO-sensitive electrode.

Conclusion: Combining NO? generated from AS with electron acceptors results in NO generation and substantial hypoxic cell radiosensitization. NO? derived from donor agents or endogenously produced in tumors, combined with electron acceptors, may provide an important strategy for radiosensitizing hypoxic cells and warrants in vivo evaluation.

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Published date: 1 November 1998
Additional Information: Presented at the 10th International Conference on Chemical Modifiers of Cancer Treatment, Clearwater, FL, Jan 28–31, 1998
Keywords: nitric oxide, nitroxyl, radiation, hypoxia, sensitizer
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337884
ISSN: 0360-3016
PURE UUID: d8512db1-13b0-4353-b9bf-e34e0d610fdb
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 29 Jun 2012 11:34
Last modified: 18 Jul 2017 06:00

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Author: James B. Mitchell
Author: William DeGraff
Author: Sungmee Kim
Author: John A. Cook
Author: Janet Gamson
Author: Danae Christodoulou
Author: Martin Feelisch ORCID iD
Author: David A. Wink

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