Comparison of the survival of directly irradiated cells and cells exposed to medium containing bystander factors after over 50 cell doublings

Full text: The bystander effect is a mechanism by which cells exposed to high or low LET radiation can either transmit the damage to neighbouring unhit cells or can transmit the damage through the cell medium to unirradiated cells. The bystander effect has been shown to produce a variety of endpoints, including cell death, changes in gene expression and chromosomal aberration. The bystander effect may increase the risk of exposure to a low dose of radiation. According to the UNSCEAR 2000 report only doses above 100 mGy will produce significant increase in risk for most tumour types in man and it is only in utero that a significant induction in tumour size has been found for doses in the 10-20 mGy range. This research indicates that ICCM (irradiated cell conditioned medium) from cells irradiated at 5mGy can induce effects in non exposed cells including, Ca2+ intracellular flux, altered survival and increased production of heat shock proteins and other proteins associated with apoptosis induction. Epigenetic changes (de-novo methylation) as a result of exposure to 5mGy ICCM have also been seen to be induced by 5 mGy ICCM. The effects persist and have been detected in progeny of cells at least 50 population doublings after the progenitors were exposed to the ICCM. While these effects do not prove that the risk of cancer induction in vivo is increased at low doses, any perturbation of pathways involved in the life or death sectoring decisions made by cells after exposure to DNA damaging agents, may impact on the number of mutations (including those involved in cancer progression) which can be perpetuated in cell populations