Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect

Abstract

Evidence accumulated over the past two decades has indicated that exposure of cell populations to ionizing radiation results in significant biological effects occurring in both the irradiated and nonirradiated cells in the population. This phenomenon, termed the 'bystander response', has been shown to occur both in vitro and in vivo and has been postulated to impact both the estimation of risks of exposure to low doses/low fluences of ionizing radiation and radiotherapy. Several mechanisms involving secreted soluble factors, oxidative metabolism and gapjunction intercellular communication have been proposed to regulate the radiation-induced bystander effect. Our current knowledge of the biochemical and molecular events involved in the latter two processes is reviewed in this article.

Cell-interdependent cisplatin killing by Ku/DNA-dependent protein kinase signaling transduced through gap junctions

“…In this phenomenon, IR-damaged cells pass a signal to unirradiated cells, triggering certain signaling pathways and producing genomic instability and cytotoxicity in the untreated cells (33)(34)(35)(36). It is also known that toxic metabolites of pro-drugs can also be passed between cells through gap junctions [for example, 5-fluorouracil that has been converted from 5-fluorocytosine by cytosine deaminase (37)].…”

Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice

“…Radiation exposure, in addition to inducing an acute damage response, also has a strong component of heritable instability, detected using in vitro immortalized cell systems , and in hematopoietic stem cells (Kadhim et al, 1992). The specific mechanisms involved are unclear, but continuous generation of reactive oxygen species has been proposed to be one of the factors responsible (Azzam et al, 2003).…”

Some problems and errors in cytogenetic biodosimetry

“…This phenomenon (bystander effect) is usually explained by cell-cell signalling between irradiated cells and closely located non-irradiated cells. Specifically, the bystander effect has been attributed to communication between irradiated and unirradiated cells by direct contact between neighbouring cells; signalling via specific substances in the nutrient medium of irradiated cells that influenced unirradiated cells and immunity-mediated responses [43,60,61]. Microarray studies revealed that the profile of gene expression in irradiated cells was different from that in unirradiated cells which exhibited evidence of bystander effect, with only part of the genes whose expression has been modulated in the irradiated cells being altered in unirradiated cells receiving media from irradiated cells [62].…”