Biomedical Engineering Reference
In-Depth Information
tissues. Similar advances have occurred in experimental studies. In particular,
the development of microbeams allow precise doses of radiation to be delivered
with high spatial accuracy into experimental models. They have evolved through
recent advances in imaging, software and beam delivery to be used in a range of
experimental studies probing spatial, temporal and low dose aspects of radiation
response [
1
]. A range of microbeams have been developed worldwide which
include ones capable of delivering charged particles, X-rays and electrons. Localised
delivery of radiation at the subcellular level is proving a powerful tool. For example,
localized production of radiation-induced damage in the nucleus allows probing of
the key mechanisms of DNA damage sensing, signalling and repair. Crucially this
can be done under conditions where cells retain viability and where the responses
to relevant environmental, occupational or clinical doses can be tested. These
approaches have started to unravel some of the early events which occur after
localised DNA damage within cells.
The key rational for the development of modern microbeams originally came
from the necessity to evaluate the biological effects of very low doses of radiation
(down to exactly one particle track traversal) in order to evaluate environmental
and occupational radiation risks. At these levels, only a few cells in the human
body are exposed [
2
] separated by intervals of months or years. Due to the
uncertainties of conventional irradiations and random Poisson distribution of tracks,
such dose patterns cannot be simulated
in vitro
using conventional broad field
techniques. Current excess cancer risks associated with exposure to very low
doses of ionizing radiation are therefore estimated by extrapolating high dose data
obtained from
in vitro
experiments or from epidemiological data from the atomic
bomb survivors. This approach, however, suffers from limited statistical power and
is unable to resolve uncertainties from confounding factors forcing the adoption
of the precautionary linear non-threshold (LNT) model. Confounding this, there is
experimental evidence of non-linear effects at low doses. These include genomic
instability [
3
], low dose hypersensitivity [
4
] and the bystander effect [
5
,
6
], which
could potentially increase the initial radiation risk, while effects such as the adaptive
response [
7
] may act as a protective mechanism reducing the overall risks at low
doses. Microbeams allow accurate targeting of single cells and analysis of the
induced damage on a cell-by-cell basis which is critical to assess the shape of the
dose-response curve in the low dose region. Using microbeams, it has been possible
to determine the effect of single particle track traversals for a range of biological
endpoints including oncogenic transformation [
8
], micronuclei formation [
9
]and
genetic instability [
10
].
23.2
Microbeam development
The development of microbeams is not new and has been an ongoing process over
many years with the first UV microbeam being described by Chahotin back in 1912
[
11
]. However, it has been with the advances in imaging, computing and radiation
