Baker-Groberg Sandra M, Bornstein Sophia, Zilberman-Rudenko Jevgenia, Schmidt Mark, Tormoen Garth W, Kernan Casey, Thomas Charles R, Wong Melissa H, Phillips Kevin G, McCarty Owen J T
Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
Cell Mol Bioeng. 2015 Sep 1;8(3):517-525. doi: 10.1007/s12195-015-0393-8. Epub 2015 May 7.
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Although there are numerous treatment options for HNSCC, such as surgery, cytotoxic chemotherapy, molecularly targeted systemic therapeutics, and radiotherapy, overall survival has not significantly improved in the last 50 years. This suggests a need for a better understanding of how these cancer cells respond to current treatments in order to improve treatment paradigms. Ionizing radiation (IR) promotes cancer cell death through the creation of cytotoxic DNA lesions, including single strand breaks, base damage, crosslinks, and double strand breaks (DSBs). As unrepaired DSBs are the most cytotoxic DNA lesion, defining the downstream cellular responses to DSBs are critical for understanding the mechanisms of tumor cell responses to IR. The effects of experimental IR on HNSCC cells beyond DNA damage are ill-defined. Here we combined label-free, quantitative phase and fluorescent microscopy to define the effects of IR on the dry mass and volume of the HNSCC cell line, UM-SCC-22A. We quantified nuclear and cytoplasmic subcellular density alterations resulting from 8 Gy X-ray IR and correlated these signatures with DNA and γ-H2AX expression patterns. This study utilizes a synergistic imaging approach to study both biophysical and biochemical alterations in cells following radiation damage and will aid in future understanding of cellular responses to radiation therapy.
头颈部鳞状细胞癌（HNSCC）是全球第六大癌症死因。尽管HNSCC有多种治疗选择，如手术、细胞毒性化疗、分子靶向全身治疗和放疗，但在过去50年中总体生存率并未显著提高。这表明需要更好地了解这些癌细胞如何对当前治疗产生反应，以改善治疗模式。电离辐射（IR）通过产生细胞毒性DNA损伤促进癌细胞死亡，包括单链断裂、碱基损伤、交联和双链断裂（DSB）。由于未修复的DSB是最具细胞毒性的DNA损伤，确定对DSB的下游细胞反应对于理解肿瘤细胞对IR的反应机制至关重要。实验性IR对HNSCC细胞的影响，除了DNA损伤外，尚不明确。在这里，我们结合无标记、定量相和荧光显微镜来确定IR对HNSCC细胞系UM-SCC-22A的干质量和体积的影响。我们量化了8 Gy X射线IR导致的细胞核和细胞质亚细胞密度变化，并将这些特征与DNA和γ-H2AX表达模式相关联。本研究采用协同成像方法来研究辐射损伤后细胞中的生物物理和生化变化，并将有助于未来对细胞对放射治疗反应的理解。
