title: Fractionated radiation exposure amplifies the radioresistant nature of prostate cancer cells.
abstract: The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60 Gy. This process selected for 22Rv1-cells with increased clonogenic survival following subsequent radiation exposure but increased sensitivity to Docetaxel. This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy.
authors.affiliation: Radiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Discipline of Radiation Therapy, Institute of Molecular Medicine, Trinity College Dublin, Ireland.
authors.forename: N
authors.initials: N
authors.lastname: McDermott
authors.affiliation: Radiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Discipline of Radiation Therapy, Institute of Molecular Medicine, Trinity College Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Meunier
authors.affiliation: Radiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Discipline of Radiation Therapy, Institute of Molecular Medicine, Trinity College Dublin, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Mooney
authors.affiliation: Department of International Health, Mount Sinai School of Medicine, New York, USA.
authors.forename: G
authors.initials: G
authors.lastname: Nortey
authors.affiliation: Department of International Health, Mount Sinai School of Medicine, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hernandez
authors.affiliation: Radiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Discipline of Radiation Therapy, Institute of Molecular Medicine, Trinity College Dublin, Ireland.|Molecular Medicine, Department Clinical Medicine, Trinity College Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Hurley
authors.affiliation: Department of Surgery, Trinity College Dublin, Ireland.
authors.forename: N
authors.initials: N
authors.lastname: Lynam-Lennon
authors.affiliation: Department of Cancer Studies &Cancer Research UK Leicester Centre, University of Leicester, UK.
authors.forename: S H
authors.initials: SH
authors.lastname: Barsoom
authors.affiliation: Department of Cancer Studies &Cancer Research UK Leicester Centre, University of Leicester, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Bowman
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, 3811 W. Thirteen Mile Road, Royal Oak, MI 48073, USA.
authors.forename: B
authors.initials: B
authors.lastname: Marples
authors.affiliation: Department of Cancer Studies &Cancer Research UK Leicester Centre, University of Leicester, UK.
authors.forename: G D D
authors.initials: GD
authors.lastname: Jones
authors.affiliation: Radiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Discipline of Radiation Therapy, Institute of Molecular Medicine, Trinity College Dublin, Ireland.
authors.forename: L
authors.initials: L
authors.lastname: Marignol
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D019583:Dose Fractionation, Radiation; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000187:drug effects; D017382:Reactive Oxygen Species; D016196:S Phase / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D043823:Taxoids; D000077143:Docetaxel