Out-of-field cell survival following exposure to intensity-modulated radiation fields.

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Butterworth KT, McGarry CK, Trainor C, O'Sullivan JM, Hounsell AR, Prise KM

Out-of-field cell survival following exposure to intensity-modulated radiation fields.

Int J Radiat Oncol Biol Phys. 2011 Apr 1;79(5):1516-22. doi: 10.1016/j.ijrobp.2010.11.034. Epub 2011 Jan 27.

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21277116 [ View in PubMed

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Abstract

PURPOSE: To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication. METHODS AND MATERIALS: Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator. RESULTS: Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the out-of-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the alpha-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response. CONCLUSIONS: These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pimagedine	Nitric oxide synthase, inducible	Protein	Humans	Yes	Inhibitor Downregulator	Details