Effects of X-RAY Irradiation on Natural Killer (NK) Cell System. L Elevation of Sensitivity of Tumor Cells and Lytic Function of NK Cells

Abstract

The in vitro effect of X-ray irradiation on the human natural killer (NK) system was studied. When K562 cells were irradiated with X-rays and cultured for 18 hours, they showed increased sensitivity to lysis by blood lymphocytes and purified large granular lymphocytes (LGL). The X-ray-induced augmentation was observed as little as 2 Gy irradiation, reaching maximum at 5 to 20 Gy. The doses of X-rays did not influence the viability and spontaneous release of the target cells. On the other hand, irradiation with X-rays of NK cells at 5 to 15 Gy resulted in a transient increase in NK activity at 1 hour, and then the activity declined and was completely lost after 24 hours. However, when LGL were cultured with interferon immediately after irradiation, they maintained elevated NK activity. These results suggest the possible use of low doses of X-ray irradiation in combination with biological response modifiers for treatment of cancer.

Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated

“…The definition of abscopal effect comes from the Latin ab (position away from) and scopus (mark or target). The abscopal mechanism of action remains unexplained, although a variety of underlying biologic events can be hypothesized, including a possible role for the immune system (25,26). The abscopal effect, however, is not often observed, possibly because many tumor-bearing hosts develop impaired DC function (reviewed in Reference 27).…”

Elevated sphingomyelinase activity and ceramide concentration in serum of patients undergoing high dose spatially fractionated radiation treatment: Implications for endothelial apoptosis

“…Importantly, elevation in circulating TNF-α levels has been found to coincide with the regression of a distant, nonirradiated hepatocellular carcinoma. 7 Experiments in nude mice further show that abscopal effects can be mediated by the immune system 8 and might target the vascular endothelium. Abscopal effects of radiation were not observed in mice lacking p53 or mice with inhibited p53, even when the implanted tumors had functional p53.…”

Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect

“…Oxidative-stress mediators have also been implicated in abscopal effects, whereby cytotoxic effects are observed in solid tumors located at distant sites from those targeted by radiation. It is thought that such effects are mediated by redox-sensitive cytokines that are cytotoxic (Ohba et al, 1998) or capable of mediating a systemic antitumor effect through the activation of immune activity (Uchida et al, 1989). Furthermore, genomic instability in the progeny of cells surviving a radiation exposure has been associated with intracellular oxidants, oxidative DNA base damage and vulnerability to free radical membrane damage (Clutton et al, 1996).…”