Synchrotron FTIR shows evidence of DNA damage and lipid accumulation in prostate adenocarcinoma PC-3 cells following proton irradiation

•Synchrotron FTIR provides a new approach to investigate proton damage in single cells.•Changes were observed in phosphodiester region consistent with changes in DNA.•Evidence of lipid deposition and chromatin condensation in cells exposed to protons.•Such changes reflect an increase in lipid metabolism during apoptosis.

Synchrotron Radiation Fourier Transform Infrared (SR-FTIR) spectra of single human prostate adenocarcinoma PC-3 cells, irradiated with a defined number of 2 MeV protons generated by a proton microbeam along with non-irradiated control cells, were analysed using multivariate methods. A number of different Principal Component Analysis (PCA) models were tested and the spectral ranges associated with nucleic acids, proteins and lipids were analysed separately. The results show a dose dependent shift of the OPO asymmetric stretching mode from 1234 cm−1 to 1237 cm−1, consistent with local disorder in the B-DNA conformation along with a change in intensity of the OPO symmetric stretching band at 1083 cm−1 indicative of chromatin fragmentation – the natural consequence of a high number of DNA Double Strand Breaks (DSBs). 2D mapping of characteristic functional groups at the diffraction limit shows evidence of lipid deposition and chromatin condensation in cells exposed to protons indicative of cell apoptosis following irradiation. These studies lay the foundation for understanding the macromolecular changes that occur to cells in response to radiation therapy, which has important implications in the treatment of tumours.