title: Time and Cell Type Dependency of Survival Responses in Co-cultured Tumor and Fibroblast Cells after Exposure to Modulated Radiation Fields.
abstract: Advanced radiotherapy techniques such as intensity-modulated radiation therapy (IMRT) achieve high levels of conformity to the target volume through the sequential delivery of highly spatially and temporally modulated radiation fields, which have been shown to impact radiobiological response. This study aimed to characterize the time and cell type dependency of survival responses to modulated fields using single cell type (SCT) and mixed cell type (MCT) co-culture models of transformed fibroblast (AG0-1522b) cells, prostate (DU-145) and lung (H460) cancer cells. In SCT cultures, in-field responses showed no significant time dependency while out-of-field responses occurred early, and plateaued 6 h after irradiation in both DU-145 and H460 cells. Under modulated beam configurations MCT co-cultures showed cell-specific, differential out-of-field responses depending on the irradiated in-field and responding out-of-field cell type. The observed differential out-of-field responses may be due to the genetic background of the cells, in particular p53 status, which has been shown to mediate radiation-induced bystander effects (RIBEs). These data provide further insight into the radiobiological parameters that influence out-of-field responses, which have potential implications for advanced radiotherapy modalities and may provide opportunities for biophysical optimization in radiotherapy treatment planning.
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;
authors.forename: Karl T
authors.initials: KT
authors.lastname: Butterworth
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;|d  Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McMahon
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;
authors.forename: Jamie C
authors.initials: JC
authors.lastname: McKee
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;
authors.forename: Gaurang
authors.initials: G
authors.lastname: Patel
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;
authors.forename: Mihaela
authors.initials: M
authors.lastname: Ghita
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;|b  Clinical Oncology and.
authors.forename: Aidan J
authors.initials: AJ
authors.lastname: Cole
authors.affiliation: c  Radiotherapy Physics, Northern Ireland Cancer Centre, Belfast, Northern Ireland, United Kingdom; and.
authors.forename: Conor K
authors.initials: CK
authors.lastname: McGarry
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;|b  Clinical Oncology and.
authors.forename: Joe M
authors.initials: JM
authors.lastname: O'Sullivan
authors.affiliation: c  Radiotherapy Physics, Northern Ireland Cancer Centre, Belfast, Northern Ireland, United Kingdom; and.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Hounsell
authors.affiliation: a  Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D018920:Coculture Techniques; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000528:radiation effects*; D006801:Humans; D015398:Signal Transduction / Q000528:radiation effects; D013997:Time Factors; D059016:Tumor Microenvironment / Q000528:radiation effects