Indirect influences of radiation on unirradiated cells through irradiated cells.

There has been a recent upsurge of interest in radiation-induced bystander effects. Previously we reported that the accumulation of inducible nitric oxide (NO) synthase (iNOS) was induced only in human glioblastoma mutant (m) p53 cells by acute irradiation with X-rays, suggesting a suppression of iNOS induction after acute irradiation with X-rays in wtp53 cells. NO secreted from the irradiated mp53 cells induced the accumulation of p53 in unirradiated wtp53 cells. The radiosensitivity of wtp53 cells was reduced by exposure to the conditioned medium from irradiated mp53 cells, suggesting that NO is an initiator of radiation-induced bystander effects. In the present study, we found that the accumulation of iNOS in wtp53 cells was induced by chronic irradiation with gamma-rays followed by acute irradiation with X-rays, but not by each one. It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation. We found that chronic irradiation with gamma-rays did not inhibit the accumulation of p53 after exposure to the conditioned medium from the irradiated mp53 cells. However, the decay of accumulated p53 was stimulated by chronic irradiation with gamma-rays. At the same time, the accumulation of Hdm2 was observed; suggesting that chronic irradiation with gamma-rays may stimulate the degradation of p53 accumulated by NO-mediated bystander effects.