Page 83 - 2014 Printable Abstract Book
P. 83
(S2202) The evolution of microbeam research. Kevin M. Prise, Centre for Cancer Research & Cell Biology,
Belfast, United Kingdom
The development of sophisticated ionizing radiation-based microbeams has been a major advance in
radiation biology. They allow individual tracks of radiation to be controlled in time and space to allow
biological responses to radiation exposure to be followed on a cell by cell basis. Microbeams involve the
coupling of sophisticated imaging, cell positioning and radiation detection technologies with individual
cell assays. For low dose studies, they allow the effects of single radiation tracks to be determined without
the complication of the Poisson distribution inherent in conventional exposures. Several microbeams are
now operational worldwide and these include not only systems which deliver charged particles, but X-
rays and electrons also. They have been used extensively for probing radiation mechanisms at the cellular
and subcellular level. Radiation-induced bystander responses are observed when non-exposed cells
respond to signals released from their irradiated neighbors. These have been observed in a range of cell
types and for different endpoints including mutations, chromosome damage, cell killing, apoptosis and
cell transformation. Many experimental approaches have been used to study bystander responses,
however microbeams offer a powerful option as they allow individual cells within populations to be easily
selected, irradiated and their responses followed after exposure. Increasingly they are being used for
targeting more complex tissue models and even whole organisms. Using these approaches, new
mechanistic information is being obtained which will allow the bystander response to be fully elucidated,
with the prospect in future of mechanistic studies in vivo.
(S2203) Bystander effects as manifestation of intercellular communication of DNA damage and of the
cellular oxidative status. George Iliakis; Holger Klammer; and Emil Mladenov, University of Duisburg-
Essen Medical School, Essen, Germany
It is becoming increasingly clear that cells exposed to ionizing radiation (IR) and other genotoxic agents
(targeted cells) can communicate their DNA damage response (DDR) status to cells that have not been
directly irradiated (bystander cells). The term radiation-induced bystander effects (RIBE) describes facets
of this phenomenon, but its molecular underpinnings are incompletely characterized. Consequences of
DDR in bystander cells have been extensively studied and include transformation and mutation induction;
micronuclei, chromosome aberration and sister chromatid exchange formation; as well as modulations in
gene expression, proliferation and differentiation patterns. A fundamental question arising from such
observations is why targeted cells induce DNA damage in non-targeted, bystander cells threatening thus
their genomic stability and risking the induction of cancer. We will review and synthesize available
literature to gather support for a model according to which targeted cells modulate as part of DDR their
redox status and use it as a source to generate signals for neighboring cells. Such signals can be either
small molecules transported to adjacent non-targeted cells via gap-junction intercellular communication
(GJIC), or secreted factors that can reach remote, non-targeted cells by diffusion or through the
circulation. We review evidence that such signals can induce in the recipient cell modulations of redox
status similar to those seen in the originating targeted cell - occasionally though self-amplifying feedback
loops. The resulting increase of oxidative stress in bystander cells induces, often in conjunction with DNA
replication, the observed DDR-like responses that are at times strong enough to cause apoptosis. We
reason that RIBE reflect the function of intercellular communication mechanisms designed to spread
within tissues, or the entire organism, information about DNA damage inflicted to individual, constituent
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Belfast, United Kingdom
The development of sophisticated ionizing radiation-based microbeams has been a major advance in
radiation biology. They allow individual tracks of radiation to be controlled in time and space to allow
biological responses to radiation exposure to be followed on a cell by cell basis. Microbeams involve the
coupling of sophisticated imaging, cell positioning and radiation detection technologies with individual
cell assays. For low dose studies, they allow the effects of single radiation tracks to be determined without
the complication of the Poisson distribution inherent in conventional exposures. Several microbeams are
now operational worldwide and these include not only systems which deliver charged particles, but X-
rays and electrons also. They have been used extensively for probing radiation mechanisms at the cellular
and subcellular level. Radiation-induced bystander responses are observed when non-exposed cells
respond to signals released from their irradiated neighbors. These have been observed in a range of cell
types and for different endpoints including mutations, chromosome damage, cell killing, apoptosis and
cell transformation. Many experimental approaches have been used to study bystander responses,
however microbeams offer a powerful option as they allow individual cells within populations to be easily
selected, irradiated and their responses followed after exposure. Increasingly they are being used for
targeting more complex tissue models and even whole organisms. Using these approaches, new
mechanistic information is being obtained which will allow the bystander response to be fully elucidated,
with the prospect in future of mechanistic studies in vivo.
(S2203) Bystander effects as manifestation of intercellular communication of DNA damage and of the
cellular oxidative status. George Iliakis; Holger Klammer; and Emil Mladenov, University of Duisburg-
Essen Medical School, Essen, Germany
It is becoming increasingly clear that cells exposed to ionizing radiation (IR) and other genotoxic agents
(targeted cells) can communicate their DNA damage response (DDR) status to cells that have not been
directly irradiated (bystander cells). The term radiation-induced bystander effects (RIBE) describes facets
of this phenomenon, but its molecular underpinnings are incompletely characterized. Consequences of
DDR in bystander cells have been extensively studied and include transformation and mutation induction;
micronuclei, chromosome aberration and sister chromatid exchange formation; as well as modulations in
gene expression, proliferation and differentiation patterns. A fundamental question arising from such
observations is why targeted cells induce DNA damage in non-targeted, bystander cells threatening thus
their genomic stability and risking the induction of cancer. We will review and synthesize available
literature to gather support for a model according to which targeted cells modulate as part of DDR their
redox status and use it as a source to generate signals for neighboring cells. Such signals can be either
small molecules transported to adjacent non-targeted cells via gap-junction intercellular communication
(GJIC), or secreted factors that can reach remote, non-targeted cells by diffusion or through the
circulation. We review evidence that such signals can induce in the recipient cell modulations of redox
status similar to those seen in the originating targeted cell - occasionally though self-amplifying feedback
loops. The resulting increase of oxidative stress in bystander cells induces, often in conjunction with DNA
replication, the observed DDR-like responses that are at times strong enough to cause apoptosis. We
reason that RIBE reflect the function of intercellular communication mechanisms designed to spread
within tissues, or the entire organism, information about DNA damage inflicted to individual, constituent
81 | P a g e
