Radiation Induced Bystander effects in Mice given Low Doses of Radiation in vivo

Abstract

ᮀ The 'bystander effect' phenomenon has challenged the traditional framework for assessing radiation damage by showing radiation induced changes in cells which have not been directly targeted, but are neighbors to or receive medium from directly hit cells. Our group performed a range of single and serial low dose irradiations on two genetically distinct strains of mice. Bladder explants established from these mice were incubated in culture medium, which was used to measure death responses in a keratinocyte reporter system. The study revealed that the medium harvested from bladder tissues' (ITCM) from acutely irradiated C57BL6 but not Balb/c mice, was able to induce clonogenic death. Administration of a priming dose(s) before a challenge dose to both C57BL6 and Balb/c mice stimulated reporter cell survival irrespective of the time interval between dose(s) delivery. When ITCM corresponding to both strains of mice was measured for its calcium mobilization inducing ability, results showed an elevation in intracellular calcium levels that was strain dependent. This indicates that genotype determined the type of bystander signal/response that was produced after exposure to low and acute doses of radiation. However, serial exposure conditions modified bystander signal production to induce similar effects that were characterized by excessive growth.

The effect of genetic background and dose on non-targeted effects of radiation

“…Media from irradiated C57 samples has been shown to initiate calcium flux in HPV-G reporter cells , Singh et al 2011, whilst CBA irradiated and control media showed no effect on calcium flux in this system. work.…”

Embryos of the zebrafish Danio rerio in studies of non-targeted effects of ionizing radiation

“…The production of bystander factors is also known to be genetically dependent [11]. In particular, radiosensitive cell lines with small or no shoulders in their cell survival curves will generate larger bystander effects when compared with radioresistant cell lines with large shoulders in their survival curves.…”

The Role of Translational Regulation in Survival after Radiation Damage; an Opportunity for Proteomics Analysis

“…The effects neighboring cells have on one another are not always protective or mitogenic. For example, in the “radiation bystander effect” described in mammalian cell culture and mice, irradiated cells make their neighbors more prone to death [ 22 , 23 , 24 ]. Antioxidants such as L-deprenyl and lactate can inhibit the bystander effect [ 25 ], suggesting that oxidative stress and energy metabolism may be involved.…”