title: Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields.
abstract: To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. 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, and this needs to be confirmed for a wider range of cell lines and conditions.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, BT7 9AE, Belfast, UK.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Ghita
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Coffey
authors.forename: Karl T
authors.initials: KT
authors.lastname: Butterworth
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McMahon
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Schettino
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
mesh_terms: D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D019583:Dose Fractionation, Radiation; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D061986:MCF-7 Cells; D014965:X-Rays / Q000009:adverse effects*