Enhanced cytotoxic activity of macrophages and suppressed tumor metastases in mice irradiated with low doses of X-rays

We showed in our previous report that a single exposure of mice to 0.1 or 0.2 Gy X-rays led to the significant inhibition of the development of artificial tumor metastases in the lungs and that the effect was related to the enhanced activity of natural killer cells. In the present study, a possible involvement of cytotoxic macrophages in the anti-metastatic effect of the low-level X-ray exposures was investigated. We now demonstrate that irradiation of mice with either of the two low doses of X-rays significantly stimulates the macrophage-mediated cytolysis of the susceptible tumor targets and that the effect coincides with the enhanced production of nitric oxide in the collected effector cells. We also show that suppression of the in vivo function of macrophages by carrageenan eliminates the inhibitory effect of the two low doses of X-rays on the development of pulmonary tumor colonies as well as significantly suppresses the macrophage-mediated cytotoxicity and nitric oxide production. Finally, aminoguanidine added to the culture medium of the assayed macrophages not only shuts down the nitric oxide synthesis in these cells but also significantly suppresses their cytolytic activity. Overall, the obtained results indicate that inhibition of the tumor metastases by a single exposure of mice to 0.1 or 0.2 Gy X-rays results, to a large extent, from the radiation-induced stimulation of the cytocidal activity of macrophages which secrete enhanced amounts of nitric oxide.