In vitro and in vivo cytotoxic effects of nitric oxide on metastatic cells.

It has been reported that nitric oxide (NO) is tumoricidal in vitro and inhalation of NO is effective for the therapy of pulmonary hypertension. However, little attention has been addressed to the effects of inhaled NO on tumors in the lung. In the present study cytotoxic effects of NO have been investigated both in vitro and in vivo using metastatic cell lines. Viabilities of both B16 melanoma and Lewis lung carcinoma cells were decreased in the presence of S-nitroso-N-acetyl-DL-penicillamine (SNAP) in vitro and the cytotoxicity of SNAP was reduced dose-dependently by NO radical scavenger, oxyhemoglobin. To examine in vivo tumoricidal activity of NO, mice were exposed to 10-80 ppm NO gas after intravenous injection of both tumor cell lines. Intravenous injection of both cell lines produced metastatic tumor colonies in the mouse lung. However, inhaled NO did not reduce the tumor colony formation in the lung. The increase in NO concentration was accompanied by elevation of concomitant nitric dioxide concentration in exposure chambers and exposure to higher concentration of NO appeared to enhance tumor colony formation in the lung.