Inter-Relationship between Low-Dose Hyper-Radiosensitivity and Radiation-Induced Bystander Effects in the Human T98G Glioma and the Epithelial HaCaT Cell Line

Abstract

Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. At low radiation doses relatively few cells die as a direct response to radiation but secondary radiation effects such as DNA mutation or bystander effects affect many cells. Consequently it is at low radiation levels where an understanding of bystander effects is essential in designing novel therapies with superior clinical outcomes. In this article, we use a hybrid multiscale mathematical model to study the direct effects of radiation as well as radiation-induced bystander effects on both tumour cells and normal cells. We show that bystander responses play a major role in mediating radiation damage to cells at low-doses of radiotherapy, doing more damage than that due to direct radiation. The survival curves derived from our computational simulations showed an area of hyper-radiosensitivity at low-doses that are not obtained using a traditional radiobiological model.

Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects

“…Fernandez-Palomo et al . measured dose-dependence of calcium through the cellular membrane, indicating a possible link between low-dose HRS and bystander effects 73 . The report by them supports our model approach to estimate the DSB number per nucleus in NTEs and cell kill in NTEs.…”

Melanin is effective in protecting fast and slow growing fungi from various types of ionizing radiation

“…It has been quite successful at describing the data (particularly for mammalian cells) and making robust predictions over a wide range of irradiation scenarios, including dose fractionation or protraction (Brenner et al, 1998;Brenner et al, 2002). However, there is growing evidence that the inducibility of some DNA repair pathways, and the effects of inter-and intra-cellular signaling can alter the shape of the clonogenic survival dose response, particularly at radiation doses where the damage is not lethal to the majority of cells (Bauchwitz and Holloman, 1990;Singh and Krishna, 2006;Coic et al, 2008;Xue et al, 2015;Fernandez-Palomo et al, 2016). The IR model (Marples and Joiner, 1993) which assumes that cells become progressively more radioresistant as radiation dose increases, is a convenient and mechanistically-plausible approach for accounting for the effects of these factors on the survival dose response.…”

Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease

“…The radiation-induced bystander effect occurs when nonirradiated cells display phenotypes and molecular gene expression signatures similar to neighboring irradiated cells. Irradiated cells utilize a wide variety of intercellular mechanisms to transmit signals to neighboring nonirradiated cells, including calcium signaling, intercellular communication machinery such as gap junctional proteins, and potent growth factors like TGFb1 (124)(125)(126)(127). There are numerous published studies, which also implicate ROS in the induction of radiation-induced bystander effects (128,129).…”