Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: A cell line study in four glioblastoma multiforme (GBM) cell lines. (December 2013)

• Record Type: Journal Article
• Authors: Schoenherr, Diane; Krueger, Sarah A.; Martin, Lynn; Marignol, Laure; Wilson, George D.; Marples, Brian
• Is Part Of: International journal of radiation biology. Volume 89:Number 12(2013:Dec.)
• Page Start: 1009
• Page End: 1016
• Publication Date: 2013-12
• Subjects: Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.3109/09553002.2013.825061
• Languages: English
• ISSNs: 0955-3002

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: To determine if ultra-fractionation using repeated pulses of radiation (10 × 0.2 Gray [Gy]) would be more cytotoxic than continuously-delivered radiation to the same total dose (2 Gy) in four glioma cell lines.</p> <p> <italic>Materials and methods</italic>: Human T98G, U373, U87MG and U138MG cells were conventionally X-irradiated with 0.1–8 Gy and clonogenic survival assessed. Next, cells were treated with either a single dose of 2 Gy or 10 pulses of 0.2 Gy using a 3-min inter-pulse interval and DNA (Deoxyribonucleic acid) repair (pHistone H2A.X), G2-phase cell cycle checkpoint arrest (pHistone H3) and apoptosis (caspase-3) compared between the two regimens. A dose of 0.2 Gy was selected as this reflects the hyper- radiosensitivity (HRS)/increased radioresistance (IRR) transition point of the low-dose cell survival curve.</p> <p> <italic>Results</italic>: T98G, U87MG and U138MG exhibited distinct HRS responses and survival curves were well-described by the Induced Repair model. Despite the prolonged delivery time, ultra-fractionation (10 × 0.2 Gy) was equally effective as a single continuously-delivered 2 Gy dose. However, ultra-fractionation was more effective when given for five consecutive days to a total dose of 10 Gy. The increased effectiveness of ultra-fractionation could not be attributed directly to differences in DNA damage, repair processes or radiation-induced apoptosis.</p> <p> <italic>Conclusions</italic>: Ultra-fractionation (10 × 0.2 Gy) is an effective modality for killing glioma cell lines compared with standard 2 Gy dosing when multiple days of treatment are given.</p> </abstract>