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Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields.

Ghita, M*; Coffey, C B*; Butterworth, K T*; McMahon, S J*; Schettino, G; Prise, K M* (2016) Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields. Phys. Med. Biol., 61 (2). pp. 515-526.

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Abstract

Radiation therapy treatment is usually performed in a fractionated regime whereby the dose required to kill tumour cells is given in several sessions spaced by specific time intervals. Previous in vitro studies have shown significant changes in the out-of-field responses due to signalling effects at typical radiotherapy doses. Whether the non-irradiated tissue would be receiving signals to respond to each fraction as a unique dose or if there would be recovery or adaptation between the fractions is still unclear. This work proposes two in vitro cell models to evaluate the direct and indirect effect of fractionated radiation delivery.
AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells were used to evaluate the in-field/out-of-field effects of fractionated radiation delivery, using conventional 225 kVp X-rays either under uniform conditions or where 50% of the cells were shielded. The experiments were carried out for acute dose delivery, and for two equal fractions delivered with time intervals from 4 h to 48 h.
For uniform exposures both cell lines show an increase in survival after the fractionated dose delivery for all time intervals between fractions. In contrast, delivery of a modulated exposure shows very limited recovery for the in-field cells. For both cell models the out-of-field response could be reduced by the addition of the radical scavenger DMSO.
DNA damage assays, measuring 53BP1 foci kinetics indicate the fast component of DNA repair is affected by fractionation in the directly exposed population.
Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule.

Item Type: Article
Subjects: Ionising Radiation
Ionising Radiation > Dosimetry
Identification number/DOI: 10.1088/0031-9155/61/2/515
Last Modified: 02 Feb 2018 13:13
URI: http://eprintspublications.npl.co.uk/id/eprint/6988

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