Harder Samantha J, Matthews Quinn, Isabelle Martin, Brolo Alexandre G, Lum Julian J, Jirasek Andrew
University of Victoria, Department of Physics and Astronomy, PO Box 1700 STN CSC, Victoria, British Columbia V8W 2Y2, Canada.
Appl Spectrosc. 2015;69(2):193-204. doi: 10.1366/14-07561. Epub 2015 Jan 1.
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.
个性化放射治疗（RT）的发展引发了人们对确定患者特异性肿瘤和正常组织对辐射反应的浓厚兴趣。拉曼光谱（RS）是一种非侵入性且无需标记的技术，可通过评估肿瘤细胞中辐射诱导的生化变化来检测辐射反应。在当前研究中，单细胞RS在四种人类上皮肿瘤细胞系中识别出特定的辐射诱导反应，这些细胞系包括肺癌（H460）、乳腺癌（MCF-7、MDA-MB-231）和前列腺癌（LNCaP），它们接受了临床剂量的辐射（2-10 Gy）。在低辐射剂量（2 Gy）下，H460和MCF-7细胞系显示糖原相关光谱特征增加，而LNCaP细胞系显示与膜磷脂相关的辐射反应。在这些细胞系中，使用主成分分析（PCA）识别辐射相关特征仅需要来自接受10 Gy或更低剂量群体的光谱信息。相比之下，MDA-MB-231细胞系在6 Gy或更高剂量下蛋白质相对于核酸和脂质光谱特征显著增加，PCA需要高剂量信息（30、50 Gy）才能识别这种生物学反应。发现暴露于临床剂量的细胞中发生的辐射相关变化的生化性质按p53状态和辐射敏感性进行分类。此外，发现RS在识别接受治疗剂量辐射的人类肿瘤细胞中的生物学反应的效用受辐射反应诱导的生化变化程度的支配，因此是细胞系特异性的。这项研究的结果证明了单细胞RS在识别和测量暴露于标准放疗剂量的肿瘤细胞中的生物学反应方面的效用和有效性。
