A comparison of the physical radiation-induced bystander effect and peroxide-mediated oxidative stress in human and murine epithelial cells

Abstract

The effects of low doses of ionizing radiation on living things is a continually evolving area of research. Importantly, low dose effects were historically overlooked and not properly accounted for the assessment of risk to human health, as is the case with the contentious linear no-threshold model. These low dose effects are now known to be relevant to human health in both accidental and intentional exposures, including doses relevant to medical diagnostics and therapeutics. Furthermore, there is a relative dearth of information on low dose effects in non-human species, which necessitates further investigation and evaluation of radiosensitivity. Radiation-induced bystander effects occur in organisms due to the receipt of signals from directly irradiated cells, which act to communicate radiation damage to surrounding cells. Recent research has identified one type of bystander signal which is carried by photons of biological origin, however the effects produced in bystander cells receiving these photons has not been extensively investigated. It was suspected, based on previous research, that reactive oxygen species participate in the manifestation of this bystander effect. Three mammalian cell lines were assessed for their ability to produce bystander photons upon direct irradiation; subsequently, radiologically unexposed cells were exposed to the resulting photons and assayed for biological effects. The human cell lines used exhibited significant photon emissions and oxidative stress, clonogenic cell death, reduced cellular metabolism, and compromised mitochondrial oxidative phosphorylation following exposure to these photons. The use of a melanocyte cell line indicated that these effects are attenuated by melanin, and this is suspected to occur through photoabsorption or antioxidant mechanisms. Additionally, the same assays were conducted following cell exposure to hydrogen peroxide at low concentrations to assess responses to oxidative stress relevant to bystander responses, indicating less overall sensitivity in the examined melanocytes. These findings are significant because they contribute to our understanding of the mechanisms behind low dose biological effects, because they further challenge the linear no-threshold model and other models based on target theory, because they provide evidence for differential responses to the physical bystander signal in non-human species, and because secondary photon emissions are likely relevant to the medical radiation sciences.