Keywords: low doses, X-rays, NK cells, macrophages, cytotoxicity, nitric oxide
Inhibition of the development of pulmonary tumour nodules and stimulation of the activity of NK cells and macrophages in mice by single low doses of low-LET radiation
As indicated by a few recent reports, exposures to low doses of ionising radiation can trigger the activity of natural anti-tumour defence mechanisms and impede the development of transplantable tumours in rodents. In our experimental system, BALB/c mice were irradiated with a single dose of 0.1, 0.2, 0.5, or 1.0 Gy X-rays and then i.v. injected with L1 sarcoma cells. As shown by the results of the lung-colony assay the number of tumour nodules was significantly reduced in the animals exposed to 0.2 Gy in comparison to those irradiated with 0.5 and 1.0 Gy X-rays. This effect was accompanied by the significant stimulation of the activity of NK cells obtained from the spleens of mice exposed to 0.2 and 1.0 Gy as compared to the control, non-irradiated counterparts. However, since the spleen cellularity was substantially reduced by irradiation with 1.0 but not 0.1 or 0.2 Gy and in view of the relatively low radiosensitvity of NK cells compared to B and T lymphocytes, it is possible that the stimulatory effect of 1.0 Gy X-rays resulted from the enrichment of the spleen cell population in natural killer effectors by this dose of X-rays. Moreover, i.p. injection of the anti-asialoGM1 antibody abrogated the differences between the number of tumour cell colonies in the lungs of mice exposed to 0.2 and 1.0 Gy of X-rays. Finally, peritoneal macrophages obtained from mice exposed to 0.1 or 0.2 Gy X-rays and incubated with IFNγ-synthesised significantly greater amounts of nitric oxide than macrophages collected from either the non-irradiated or the 1.0 Gy-exposed mice. However, neither the unstimulated nor the IFNγ-treated macrophages lysed the L1 sarcoma cells in the in vitro assay. The results collectively indicate that the inhibitory effect of 0.2 Gy of X-rays on the development of secondary tumour nodules in mice is associated with the stimulation by this small dose of radiation of the NK cell- and/or macrophage-mediated functions.