Mechanistic studies on radiation-induced bystander responses in human lung fibroblasts

Full text: Considerable evidence has emerged suggesting that direct nuclear damage may not be essential in mediating the genotoxic effects of radiation. Non-irradiated bystander cells have been demonstrated to exhibit responses similar to irradiated cells, especially damage corresponding to low-dose radiation exposure. Although there is evidence supporting gap junction mediated cell-cell communication and secretion of growth factors by irradiated cells as being involved in mediating the bystander effect, the nature of the signaling molecule(s) remains unclear. Utilizing specially designed mylar dishes, it was possible to separate and study non-irradiated, bystander normal human lung fibroblasts from their irradiated counterparts. The survival fraction of bystander cells, when compared with controls, decreased significantly after hit cells received a dose of 0.5 Gy alpha particles. Using cDNA expression arrays, the differentially expressed genes in bystander cells was examined at various time points following irradiation. Batch of genes involved in several signal transduction pathways were found to be altered in bystander cells. These findings will be confirmed by RT-PCR and/or Northern blot. Possible cross-linked signal transduction pathways on radiation-induced bystander effect in normal human lung fibroblasts are currently being examined. (This work was supported in part by NIH grants CA 49062, CA 75384 and the Columbia Microbeam Facility NIH Research Resource Center grant RR 11623)