Alpha-Particle-Induced Increases in the Radioresistance of Normal Human Bystander Cells

Abstract

Numerous investigators have reported that direct exposure of cells to a low dose of ionizing radiation 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 a low dose of alpha particles. Normal human lung fibroblasts (HFL-1) were irradiated with 1 cGy of alpha particles and their supernatants were transferred to unirradiated HFL-1 cells as a bystander cell model. Compared to directly irradiated cells that were not treated with supernatants from HFL-1 cells exposed to low-dose radiation, such treatment resulted in increased clonogenic survival after subsequent exposure to 10 and 19 cGy of alpha particles. Increases in protein levels of AP-endonuclease, a redox and DNA base excision repair protein, were found in the bystander cells, but not in directly irradiated cells. Supernatants from alpha-particle-irradiated cells were also found to increase the clonogenicity of unirradiated cells. These results, in conjunction with our earlier findings that supernatants from cells exposed to a low dose of alpha particles contain growth-promoting activity, suggest that this new bystander effect may be related to an increase in DNA repair and cell growth/cell cycle regulation.

The Bystander Effect: Recent Developments and Implications for Understanding the Dose Response

“…Xu et al (1996). can reduce the effects of the damaging system. Using doses where bystander effects have been shown to occur, such experiments have been reported by Iyer and Lehnert (2002a). They showed that medium taken from human lung fibroblasts exposed to 10 mGy of α-radiation increased clonogenic survival of other cells exposed to 100 mGy of α-particles.…”

DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals

“…Given that the multiple markers that have been used to study the BSE, that is, micronuclei formation (Yang et al, 2007), clonogenic survival (O'NeillMehlenbacher et al, 2007), apoptosis (Grifalconi et al, 2007) and sister chromatid exchange (SCE) (Nagasawa et al, 2005) (Figure 1), are themselves considered to be detrimental, it has been assumed that the BSE is harmful to neighboring cells. However, it has also been proposed that the BSE may actually be beneficial at a tissue level; cells exposed to a bystander signal are more radioresistant to subsequent IR-induced damage indicative of an adaptive response (Iyer and Lehnert, 2002). It is also noteworthy that of these markers, only SCE frequency is not significantly influenced by direct low-LET (for example, g-ray) radiation exposure (Ardito et al, 1980), making SCE an attractive marker of the BSE.…”

Genomic instability and bystander effects: a historical perspective

“…An increase in protein levels of AP endonuclease, a redox and DNA base excision repair protein, was also measured in bystander cells but not in directly irradiated cells. The promitogenic response was associated with an increase in cloning efficiency (Iyer and Lehnert, 2002). …”

“…The results from different laboratories, however, are not entirely consistent. Some workers report that incubation with such a conditioned medium leads to a reduction in cloning efficiency of the recipient cells (Lyng et al, 2002;Sawant et al, 2002), while others find that it is enhanced (Iyer and Lehnert, 2002) or dependent on cell type (Mothersill and Seymour, 1997). The effect of irradiated medium alone is particularly controversial.…”