Immunological mechanism of the low-dose radiation-induced suppression of cancer metastases in a mouse model

Abstract

According to the doctrine underlying the current radiation protection regulations each, no matter how small, exposure to ionizing radiation may be carcinogenic. However, numerous epidemiological observations demonstrate that cancer incidence and/or mortality are not elevated among inhabitants of the high- versus low-natural-background radiation areas and homes. Results of our own and other authors' studies described in this paper bear testimony to the possibility that stimulation of the anti-neoplastic immune surveillance mediated by NK lymphocytes and activated macrophages explains, at least partially, the accumulating epidemiological and experimental evidence indicating that low-level exposures to the low-linear energy transfer (LET) radiation inhibit the development of spontaneous and artificial metastases in humans and laboratory animals, respectively. The results presented also suggest the possibility of using low-level X- and gamma-ray exposures to cure cancer and to prevent cancer metastases. For a broader perspective, the results presented may help towards relaxing the current radiation protection regulations, especially as they apply to diagnostic and therapeutic exposures of patients to the indicated forms of radiation.

Keywords: NK cells; anti-neoplastic activity; cytotoxic macrophages; low-level X-rays; tumor lung colonies.

FIGURE 1.

Schematic outline of single exposures of BALB/c mice to X-rays (HS320 Pantak X-ray generator [230 kV, 20 mA] supplied with the Al and Cu filters, at 2.2 Gy/h dose rate) and times of the assessment of tumor lung colonies and activities of the NK cell-enriched splenocytes (NK cells) and peritoneal macrophages (Mϕ).

FIGURE 2.

Schematic outline of fractionated exposures of BALB/c mice to X-rays (ANDREX X-ray generator [150 kV, 3 mA], at 2.16 Gy/h dose rate) and times of the assessment of tumor lung colonies and activities of the NK cell-enriched splenocytes (NK cells) and peritoneal macrophages (Mϕ).

FIGURE 3.

Relative numbers (percentages of the control values indicated as solid line at 100%) of the induced tumor colonies in the lungs of BALB/c mice exposed to single (A) or fractionated (B) total doses of 0.1 or 0.2 Gy X-rays and two hours later i.v. injected with L1 sarcoma cells. Mean values ± SD (bars) are shown. *indicates statistically significant (p<0.05) difference from the control (100%) value.

FIGURE 4.

Schematic outline of the possible interactions between NK cells, macrophages, and tumor cells.