Cellular response to modulated radiation fields

Abstract

Cell survival following exposure to spatially modulated beams, as created by intensity-modulated radiotherapy (IMRT), is investigated. In vitro experiments were performed using malignant melanoma cells (MM576) exposed to a therapeutic megavoltage photon beam. We compared cell survival in modulated fields with cell survival in uniform control fields. Three different spatial modulations of the field were used: a control 'uniform' field in which all cells in a flask were uniformly exposed; a 'quarter' field in which 25% of cells at one end of the flask were exposed and a 'striped' field in which 25% of cells were exposed in three parallel stripes. The cell survival in both the shielded and unshielded regions of the modulated fields, as determined by a clonogenic assay, were compared to the cell survival in the uniform field. We have distinguished three ways in which cell survival is influenced by the fate of neighbouring cells. The first of these (type I effect) is the previously reported classical Bystander effect, where cell survival is reduced when communicating with irradiated cells. We find two new types of Bystander effect. The type II effect is an observed increase in cell survival when nearby cells receive a lethal dose. The type III effect is an increase in the survival of cells receiving a high dose of radiation, when nearby cells receive a low dose. These observations of the Bystander effects emphasize the need for improved radiobiological models, which include communicated effects and account for the effects of modulated dose distribution.

Radiation-Induced Bystander Effects in Cultured Human Stem Cells

“…In order to examine RIBE in hSC grown in media collected from directly IR-exposed hSC, we performed medium transfer studies as described in the Materials and Methods section. The doses used for irradiation, the duration of conditioning of culture medium on directly IR-exposed cells, and the length of bystander incubation were based on our previous studies and data from other groups published elsewhere [5], [19], [20], [21]. Induction of DDR was determined by formation of ionizing radiation-induced foci (IRIF) in bystander cell populations, as judged by 53BP1 [22], [23] and phospho-CHK2 analysis of hSC.…”

Radiation-induced bystander signalling in cancer therapy

“…In further studies they compared the effects of a uniform field with those when 25% of a flask was exposed either as a single region or as three parallel stripes. Survival was dependent on a complex interplay between the fraction of shielded cells and the dose to the exposed areas, again indicative of bystander signalling having a significant effect94.…”

Reactive oxygen species formation and bystander effects in gradient irradiation on human breast cancer cells

“…For example, optimized non-uniform (e.g., gradient) dose delivery to the tumor target may significantly reduce the radiation toxicity to healthy cells near the target. Cell survival can be enhanced by the less damage to neighboring cells subjected to different types of intensity-modulated radiation fields compared with uniform irradiation (UI) [5]. Tumor cells' response to non-uniform irradiation is more sensitive than traditional UI due to a different cellular communication mechanism [6].…”