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Redox generation of nitric oxide to radiosensitize hypoxic cells

Redox generation of nitric oxide to radiosensitize hypoxic cells
Redox generation of nitric oxide to radiosensitize hypoxic cells
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.
nitric oxide, nitroxyl, radiation, hypoxia, sensitizer
0360-3016
795-798
Mitchell, James B.
0c4ca906-da8c-4d12-b288-0b72a194fc2e
DeGraff, William
a9902533-652c-4773-a105-c9ec64e62b55
Kim, Sungmee
109f51ff-fed1-4c6d-9051-2f949166fd3a
Cook, John A.
18ff6e56-8ba4-4a5e-9b9e-65534461568d
Gamson, Janet
665a45f7-8e38-448b-9cea-31deedff8f4e
Christodoulou, Danae
34c70952-bf11-40d1-8635-07251ab30853
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Wink, David A.
008b5aec-8c2b-4035-8912-fb6fd530413c
Mitchell, James B.
0c4ca906-da8c-4d12-b288-0b72a194fc2e
DeGraff, William
a9902533-652c-4773-a105-c9ec64e62b55
Kim, Sungmee
109f51ff-fed1-4c6d-9051-2f949166fd3a
Cook, John A.
18ff6e56-8ba4-4a5e-9b9e-65534461568d
Gamson, Janet
665a45f7-8e38-448b-9cea-31deedff8f4e
Christodoulou, Danae
34c70952-bf11-40d1-8635-07251ab30853
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Wink, David A.
008b5aec-8c2b-4035-8912-fb6fd530413c

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), 795-798. (doi:10.1016/S0360-3016(98)00327-7). (PMID:9845098)

Record type: Article

Abstract

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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More information

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

Identifiers

Local EPrints ID: 337884
URI: http://eprints.soton.ac.uk/id/eprint/337884
ISSN: 0360-3016
PURE UUID: d8512db1-13b0-4353-b9bf-e34e0d610fdb
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 29 Jun 2012 11:34
Last modified: 15 Mar 2024 03:41

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Contributors

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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