Investigation of radiation-induced bystander effects on cancer cells using NMR metabolomics

Chen BQ1, Rogers LJ2, Esteves AIS2, McKenzie DR3, Suchowerska N2 and Kwan A1

  1. School of Life and Environmental Sciences, University of Sydney, NSW, Australia.
  2. Department of Radiation Oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia.
  3. School of Physics, University of Sydney, NSW, Australia.

Cancer is a leading cause of death and is often treated with radiotherapy. Typically, a uniform radiation dose to the target volume is prescribed, but periodically modulated doses have been shown to enhance cancer cell death relative to normal cell survival [1]. This effect has been attributed to soluble signalling molecules known as radiation-induced bystander factors [2]. Currently, these factors are not well characterised and their effects are not considered in treatment planning. Identification of these factors will shed light on the mechanism that underlies the bystander effect and improve treatment plans and patient outcomes. Metabolomics is a technique that has been frequently used for the identification and quantification of small molecules (< 1500 Da) in biofluids, but has not been directly used to study the bystander effect. We use Nuclear Magnetic Resonance (NMR) spectroscopy to examine the changes in metabolite profiles of cancer cells irradiated under uniform and spatially modulated fields, compared to unirradiated cells.We have optimised the protocol for cell collection and extraction, including comparing different extraction methods, plus NMR acquisition parameters. Differential expression of observed metabolites informs the nature of the mechanisms driving bystander effects. 1. Peng, V., et al., Grid therapy using high definition multileaf collimators: realizing benefits of the bystander effect. Acta Oncologica, 2017. 56(8): p. 1048-1059. 2. Prise, K.M. and J.M. O’Sullivan, Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer, 2009. 9(5): p. 351-60.