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Hypoxic Mammalian Cell Radiosensitization by Nitric Oxide

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

The bioregulatory molecule, nitric oxide (NO), was evaluated as a hypoxic cell radiosensitizer. Authentic NO gas was nearly as effective as oxygen in radiosensitizing hypoxic Chinese hamster V79 lung cells as evaluated using clonogenic assays. When NO was delivered to hypoxic Chinese hamster V79 cells using the NO-releasing agent (C₂H₅)₂N[N(O)-NO]^–Na⁺, radiosensitization was also observed with a sensitizer enhancement ratio of 2.4 (1 mM (C₂H₅)₂N[N(O)NO]^–Na⁺). Aerobic radiosensitivity was not affected at this concentration. The hypoxic cell radiosensitization properties of (C₂H₅)₂N[N(O)NO]^–Na⁺, coupled with the vasodilatory effects of NO on tumor vasculature, suggest that such agents open a new avenue of research in radiation oncology.

¹ To whom requests for reprints should be addressed, at Radiation Oncology Branch, National Cancer Institute, Bldg. 10, Room B3-B69, Bethesda, MD 20892.

Received 10/ 6/93. Accepted 11/ 1/93.

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