title: Genome-wide transcription responses to synchrotron microbeam radiotherapy.
abstract: The majority of cancer patients achieve benefit from radiotherapy. A significant limitation of radiotherapy is its relatively low therapeutic index, defined as the maximum radiation dose that causes acceptable normal tissue damage to the minimum dose required to achieve tumor control. Recently, a new radiotherapy modality using synchrotron-generated X-ray microbeam radiotherapy has been demonstrated in animal models to ablate tumors with concurrent sparing of normal tissue. Very little work has been undertaken into the cellular and molecular mechanisms that differentiate microbeam radiotherapy from broad beam. The purpose of this study was to investigate and compare the whole genome transcriptional response of in vivo microbeam radiotherapy versus broad beam irradiated tumors. We hypothesized that gene expression changes after microbeam radiotherapy are different from those seen after broad beam. We found that in EMT6.5 tumors at 4-48 h postirradiation, microbeam radiotherapy differentially regulates a number of genes, including major histocompatibility complex (MHC) class II antigen gene family members, and other immunity-related genes including Ciita, Ifng, Cxcl1, Cxcl9, Indo and Ubd when compared to broad beam. Our findings demonstrate molecular differences in the tumor response to microbeam versus broad beam irradiation and these differences provide insight into the underlying mechanisms of microbeam radiotherapy and broad beam.
authors.affiliation: Centre for Innate Immunity and Infectious Disease, Monash Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia. carl.sprung@monash.edu
authors.forename: Carl N
authors.initials: CN
authors.lastname: Sprung
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Yang
authors.forename: Helen B
authors.initials: HB
authors.lastname: Forrester
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.forename: Marina
authors.initials: M
authors.lastname: Zaitseva
authors.forename: Leonie
authors.initials: L
authors.lastname: Cann
authors.forename: Tina
authors.initials: T
authors.lastname: Restall
authors.forename: Robin L
authors.initials: RL
authors.lastname: Anderson
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Crosbie
authors.forename: Peter A W
authors.initials: PA
authors.lastname: Rogers
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000032:analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D005802:Genes, MHC Class II; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000532:radiotherapy*; D017356:Synchrotrons
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse