This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liebmann, J. Articles by Mitchell, J. B. Search for Related Content PubMed PubMed Citation Articles by Liebmann, J. Articles by Mitchell, J. B.

In Vivo Radiation Protection by Nitric Oxide Modulation

Radiation Biology Branch [J. L., A. M. D., D. C., J. B. M.] and Biostatistics and Data Management Section [D. V.], National Cancer Institute, Bethesda, Maryland 20892, and Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [L. K. K., D. A. W.]

Drugs that affect blood flow have been shown to be whole body radiation protectors. Using N^G-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, and the NO-releasing agent (C₂H₅)₂N[N(O)NO^-]Na⁺ (DEA/NO), we have studied the ability of NO to modulate whole body radiation toxicity in C3H mice. N^G-Nitro-L-arginine given to mice between 15 and 60 min prior to radiation afforded significant protection from whole body irradiation, e.g., the estimated whole body irradiation dose required to kill 50% of mice by 30 days after radiation (LD_50/30) in mice treated with N^G-nitro-L-arginine 60 min before irradiation was 1051 cGy compared with a whole body radiation LD_50/30 of 822 cGy in control mice (P < 0.00001). Treatment of mice with DEA/NO prior to whole body irradiation also significantly reduced toxicity; the estimated whole body radiation LD_50/30 was 1063 and 945 cGy in mice treated with DEA/NO 10 or 30 min before irradiation, respectively (P < 0.00001 for radiation LD_50/30 of either DEA/NO-treated group compared with control). Measurement of [¹⁴C]etanidazole binding to bone marrow demonstrated that DEA/NO and N^G-nitro-L-arginine exacerbated bone marrow hypoxia. Perturbations of NO levels have profound effects on in vivo radiosensitivity of normal tissues. We hypothesize that alterations in regional blood flow may underlie the changes in radiosensitivity that we have observed.

¹ To whom requests for reprints should be addressed.

Received 3/18/94. Accepted 5/16/94.

This article has been cited by other articles:

				J. B. Maxhimer, D. R. Soto-Pantoja, L. A. Ridnour, H. B. Shih, W. G. DeGraff, M. Tsokos, D. A. Wink, J. S. Isenberg, and D. D. Roberts Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling Science Translational Medicine, October 21, 2009; 1(3): 3ra7 - 3ra7. [Abstract] [Full Text] [PDF]

				J. S. Isenberg, J. B. Maxhimer, F. Hyodo, M. L. Pendrak, L. A. Ridnour, W. G. DeGraff, M. Tsokos, D. A. Wink, and D. D. Roberts Thrombospondin-1 and CD47 Limit Cell and Tissue Survival of Radiation Injury Am. J. Pathol., October 1, 2008; 173(4): 1100 - 1112. [Abstract] [Full Text] [PDF]

				C. Perrotta, L. Bizzozero, S. Falcone, P. Rovere-Querini, A. Prinetti, E. H. Schuchman, S. Sonnino, A. A. Manfredi, and E. Clementi Nitric Oxide Boosts Chemoimmunotherapy via Inhibition of Acid Sphingomyelinase in a Mouse Model of Melanoma Cancer Res., August 15, 2007; 67(16): 7559 - 7564. [Abstract] [Full Text] [PDF]