title: Radiation Promptly Alters Cancer Live Cell Metabolic Fluxes: An In Vitro Demonstration.
abstract: Quantitative data is presented that shows significant changes in cellular metabolism in a head and neck cancer cell line 30 min after irradiation. A head and neck cancer cell line (UM-SCC-22B) and a comparable normal cell line, normal oral keratinocyte (NOK) were each separately exposed to 10 Gy and treated with a control drug for disrupting metabolism (potassium cyanide; KCN). The metabolic changes were measured live by fluorescence lifetime imaging of the intrinsically fluorescent intermediate metabolite nicotinamide adenosine dinucleotide (NADH) fluorescence; this method is sensitive to the ratio of bound to free NADH. The results indicated a prompt shift in metabolic signature in the cancer cell line, but not in the normal cell line. Control KCN treatment demonstrated expected metabolic fluxes due to mitochondrial disruption. The detected radiation shift in the cancer cells was blunted in the presence of both a radical scavenger and a HIF-1α inhibitor. The HIF-1α abundance as detected by immunohistochemical staining also increased substantially for these cancer cells, but not for the normal cells. This type of live-cell metabolic monitoring could be helpful for future real-time studies and in designing adaptive radiotherapy approaches.
authors.affiliation: a   Laboratory for Optical and Computational Instrumentation, Vice Chancellor Office for Graduate Research and Education and Departments of.|b   Medical Physics and.
authors.forename: David
authors.initials: D
authors.lastname: Campos
authors.affiliation: d   Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wenny
authors.initials: W
authors.lastname: Peeters
authors.affiliation: c   Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin; and.
authors.forename: Kwangok
authors.initials: K
authors.lastname: Nickel
authors.affiliation: a   Laboratory for Optical and Computational Instrumentation, Vice Chancellor Office for Graduate Research and Education and Departments of.
authors.forename: Brian
authors.initials: B
authors.lastname: Burkel
authors.affiliation: d   Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.affiliation: c   Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin; and.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Kimple
authors.affiliation: c   Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin; and.
authors.forename: Albert
authors.initials: A
authors.lastname: van der Kogel
authors.affiliation: a   Laboratory for Optical and Computational Instrumentation, Vice Chancellor Office for Graduate Research and Education and Departments of.|b   Medical Physics and.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.affiliation: a   Laboratory for Optical and Computational Instrumentation, Vice Chancellor Office for Graduate Research and Education and Departments of.|b   Medical Physics and.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kissick
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D010101:Oxygen Consumption / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D013997:Time Factors
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit