Signaling pathway of cellular response to radiation

Radioadaptive response of cells is the induction of resistance to the moderate or high doses of radiation by previous exposure to low doses (see Ref 1). The underlying mechanisms may have a considerable impact on the cellular defence mechanisms and radiation risk. I now show by chromosome aberration analysis that the cultured mouse cells respond differently to X-ray dose below and above 0.1 Gy; higher dose is not only incapable of inducing adaptation but also rapidly extinguishes the adapted condition already induced by lower doses. Tumor promoter phorbol 12-myristate 13-acetate (PMA) and hydrogen peroxide, but not extracellular superoxide, mimicked X-rays in inducing adaptation. The over-exposure to PMA or inhibitors of protein kinase C (PKC) abrogates the adaptive response to X-rays, providing evidence for the involvement of PKC-mediated signaling pathway but distinct in its optimum dose from that for the transcriptional activation of some immediate early response genes (see Ref.3). The radioadaptive response is absent the tumorigenic variant cells but can be restored when morphologically reverted by introducing human chromosome 11, suggesting altered signaling pathways in tumour cells and downregulation by signaling pathway-specific interference. (author)