title: Effect of ionizing radiation on the physical biology of head and neck squamous cell carcinoma cells.
abstract: 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 damagein vitroare 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.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Baker-Groberg
authors.affiliation: Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Bornstein
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Jevgenia
authors.initials: J
authors.lastname: Zilberman-Rudenko
authors.affiliation: Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Garth W
authors.initials: GW
authors.lastname: Tormoen
authors.affiliation: Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Kernan
authors.affiliation: Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Thomas
authors.affiliation: Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Wong
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Phillips
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Owen J T
authors.initials: OJ
authors.lastname: McCarty
keywords: Quantitative phase microscopy; head and neck squamous cell carcinoma; physical biology; radiation damage