Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells

Numerous investigators have reported that irradiation of cells with a low dose of ionizing radiation (IR) can induce a condition of enhanced radioresistance, i.e. a radioadaptive response. In this report, we investigated the hypothesis that a radioadaptive bystander effect may be induced in unirradiated cells by a transmissible factor(s) present in the supernatants of cells exposed to low dose gamma-rays. Normal human lung fibroblasts (HFL-1) were irradiated with a 1 cGy dose of gamma-rays and their supernatants were transferred to unirradiated HFL-1 as a bystander cell model. Compared with the directly irradiated cells, such treatment resulted in increased clonogenic survival following subsequent gamma-irradiation with 2 and 4 Gy. This radioadaptive bystander effect was found to be preceded by early decreases in cellular levels of TP53 protein, increase in intracellular ROS, and increase in the redox and DNA repair protein AP-endonuclease (APE). The demonstration that radioadaptation can occur in unirradiated cells via a fluid-phase, transferable factor(s) adds to the complexity of the current understanding of mechanisms by which radioadaptive responses can be induced by low dose, low-LET IR.