title: A Raman spectroscopic study of cell response to clinical doses of ionizing radiation.
abstract: The drive toward personalized radiation therapy (RT) has created significant interest in determining patient-specific tumor and normal tissue responses to radiation. Raman spectroscopy (RS) is a non-invasive and label-free technique that can detect radiation response through assessment of radiation-induced biochemical changes in tumor cells. In the current study, single-cell RS identified specific radiation-induced responses in four human epithelial tumor cell lines: lung (H460), breast (MCF-7, MDA-MB-231), and prostate (LNCaP), following exposure to clinical doses of radiation (2-10 Gy). At low radiation doses (2 Gy), H460 and MCF-7 cell lines showed an increase in glycogen-related spectral features, and the LNCaP cell line showed a membrane phospholipid-related radiation response. In these cell lines, only spectral information from populations receiving 10 Gy or less was required to identify radiation-related features using principal component analysis (PCA). In contrast, the MDA-MB-231 cell line showed a significant increase in protein relative to nucleic acid and lipid spectral features at doses of 6 Gy or higher, and high-dose information (30, 50 Gy) was required for PCA to identify this biological response. The biochemical nature of the radiation-related changes occurring in cells exposed to clinical doses was found to segregate by status of p53 and radiation sensitivity. Furthermore, the utility of RS to identify a biological response in human tumor cells exposed to therapeutic doses of radiation was found to be governed by the extent of the biochemical changes induced by a radiation response and is therefore cell line specific. The results of this study demonstrate the utility and effectiveness of single-cell RS to identify and measure biological responses in tumor cells exposed to standard radiotherapy doses.
authors.affiliation: University of Victoria, Department of Physics and Astronomy, PO Box 1700 STN CSC, Victoria, British Columbia V8W 2Y2, Canada.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Harder
authors.forename: Quinn
authors.initials: Q
authors.lastname: Matthews
authors.forename: Martin
authors.initials: M
authors.lastname: Isabelle
authors.forename: Alexandre G
authors.initials: AG
authors.lastname: Brolo
authors.forename: Julian J
authors.initials: JJ
authors.lastname: Lum
authors.forename: Andrew
authors.initials: A
authors.lastname: Jirasek
mesh_terms: D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016158:Genes, p53; D006801:Humans; D061986:MCF-7 Cells / Q000528:radiation effects; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D025341:Principal Component Analysis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects; D011839:Radiation, Ionizing; D011879:Radiotherapy Dosage; D012815:Signal Processing, Computer-Assisted; D059010:Single-Cell Analysis / Q000379:methods; D013059:Spectrum Analysis, Raman / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D010743:Phospholipids