title: Separation of two sub-groups with different DNA content after treatment of T-47D breast cancer cells with low dose-rate irradiation and intermittent hypoxia.
abstract: Background Previous studies have shown that combined treatment with internal ultra-low dose-rate irradiation selectively inactivated hypoxic T-47D breast cancer cells after three to five weeks of treatment. However, 2-3% of the hypoxic cells were found to survive and restart proliferation upon re-oxygenation. Purpose To investigate the metastatic potential and characteristics of radiosensitivity of these surviving cells, named T - 47 DS. Material and Methods The T - 47 DScells were grown in ambient air without irradiation. A cloning experiment identified two sub-groups with different DNA content ([Formula: see text] and [Formula: see text]). Furthermore, radiosensitivity and presence of hyper-radiosensitivity (HRS) was measured by Co-60 challenge irradiation and relative migration was determined by scratch assays. Results The two subpopulations of T - 47 DShad different DNA content; one had abnormally high DNA content ([Formula: see text]) and one had DNA content similar to wild-type T-47D cells ([Formula: see text]). HRS was surprisingly present in cells of the cloned population [Formula: see text], but was absent in cells of both [Formula: see text] and T - 47 DS. The radio response of T - 47 DS, [Formula: see text] at higher radiation doses were similar to that of T-47D cells, and neither subpopulation showed increased migration compared with wild-type T-47D. Conclusion No increase in the risk of metastasis was found and only slight changes in radiosensitivity in response to conventional clinical doses was observed. Thus, the data suggest that if ultra-low dose-rate irradiation is used for targeting the hypoxic tumor fraction, conventional high dose-rate irradiation can be used to eradicate eventual surviving cells as well as cells in the well oxygenated areas of the tumor.
authors.affiliation: 1 Department of Physics, University of Oslo, Oslo, Norway.|2 Department of Medical Physics, Oslo University Hospital, Oslo, Norway.
authors.forename: Stine Gyland
authors.initials: SG
authors.lastname: Mikalsen
authors.affiliation: 1 Department of Physics, University of Oslo, Oslo, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Jeppesen Edin
authors.affiliation: 1 Department of Physics, University of Oslo, Oslo, Norway.
authors.forename: Joe Alexander
authors.initials: JA
authors.lastname: Sandvik
authors.affiliation: 1 Department of Physics, University of Oslo, Oslo, Norway.
authors.forename: Erik Olai
authors.initials: EO
authors.lastname: Pettersen
mesh_terms: D001943:Breast Neoplasms / Q000532:radiotherapy*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA; D005260:Female; D006801:Humans; D011829:Radiation Dosage; D011836:Radiation Tolerance
chemical_list: D004247:DNA
keywords: DNA analysis; T–47D cells; hyper-radiosensitivity; hypoxia; low dose-rate irradiation