Radiation microbeams as spatial and temporal probes of subcellular and tissue response

Abstract

Understanding the effects of ionising radiations are key to determining their optimal use in therapy and assessing risks from exposure. The development of microbeams where radiations can be delivered in a highly temporal and spatially constrained manner has been a major advance. Several different types of radiation microbeams have been developed using X-rays, charged particles and electrons. For charged particles, beams can be targeted with sub-micron accuracy into biological samples and the lowest possible dose of a single particle track can be delivered with high reproducibility. Microbeams have provided powerful tools for understanding the kinetics of DNA damage and formation under conditions of physiological relevance and have significant advantages over other approaches for producing localised DNA damage, such as variable wavelength laser beam approaches. Recent studies have extended their use to probing for radiosensitive sites outside the cell nucleus, and testing for mechanisms underpinning bystander responses where irradiated and non-irradiated cells communicate with each other. Ongoing developments include the ability to locally target regions of 3-D tissue models and ultimately to target localised regions in vivo. With future advances in radiation delivery and imaging microbeams will continue to be applied in a range of biological studies.

Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects

“…Taking cell culture experiments one step further, several groups have utilized a 3D reconstructed human skin culture sytem for which microbeam irradiation of a single vertical plane induced bystander effect evident at a distance of 1 mm away from targeted cells [26] and found induction of DNA damage, apoptosis, micronucleus formation, DNA hypomethylation, and senescence arrest in bystander cells [27]. An overview of microbeam experiments in tissue models of bystander effects can be found in [28]. …”

Analysis of ROP signaling in the leaf epidermis of mutant tomato with low-energy ion beam

“…Similarly, studies revealed the quantitative and temporal aspects of radiation-induced bystander mutagenesis in WTK1 human lymphoblast cells and suggested low levels of ionizing radiation-induced adaptive response were effective for reducing bystander mutagenesis through subsequent gamma-ray exposures (Zhang et al, 2009). Schettino et al (2010) reported radiation microbeam (e.g., X-rays, charged particles, and electrons) as highly spatial and temporal probes in subcellular and tissue responses.…”

Bystander Signalling: Exploring Clinical Relevance Through New Approaches and New Models

“…Technological developments have driven more sophisticated approaches using radiation microbeams allowing the delivery of highly focussed low energy micron sized radiation beams to single cells or subcellular targets. They have been successfully used as mechanistic probes to investigate biological processes including kinetics of DNA damage repair and subcellular signalling processes involved in RIBEs (13). Microbeam approaches have utilised not only ion beams, including protons and helium ions, but focussed soft X-ray microbeams and electron microbeams.…”