Page 82 - 2014 Printable Abstract Book
P. 82
S 22 HISTORICAL PERSPECTIVE: NON-TARGETED BY BYSTANDER EFFECTS, YOU DON’T HAVE TO
IRRADIATE YOUR TARGET DIRECTLY TO GET A RESPONSE
This very first "History Symposium, organized by the History committee of the Radiation Research Society,
will discuss the history and implications of non-targeted effects (NTE) which include bystander effects,
genomic instability and adaptive responses. The symposium will not only review the history but will assess
the impacts of the field on cherished paradigms in radiobiology such as the central role of DNA damage
and repair. The evolution of elegant tools including microbeams, which enable the precise study of NTE
will also be reviewed. Finally the SIT speaker will look at the future and discuss how the increasing
acceptance of the role of NTE in radiobiology is influencing modern radiobiological research.
(S2201) 100 years of bystander effects: you don’t need a DNA hit to get a response. Carmel Mothersill,
McMaster Univ, Hamilton, Canada
The last 20 years have seen what is usually referred to as a “paradigm shift” in radiobiology. This is actually
more of a “paradigm widening” than a shift because it recognizes non-targeted effects (NTE) such as
bystander effects and genomic instability as part of the response spectrum measurable after exposure of
a system to ionising radiation. As with all paradigms, the evidence for these effects was documented
almost as soon as radiation biology became a science. However due to the dominance of Muller’s fruit fly
mutation work in 1925, the emphasis was firmly placed on DNA damage as being the main way cells and
organisms were damaged by radiation. The publication of the “green pamphlet” in 1935 “On the Nature
of Gene Mutation and Gene Structure” - by the geneticist Nikolai Vladimirovich Timoféeff-Ressovsky
(1900-1981), the radiation physicist Karl Günther Zimmer (1911-1988) and the theoretical physicist Max
Delbrück (1906-1981), established target theory and left little conceptual space for the idea that hitting a
target was not necessary to produce an effect. Even the lack of heritable damage or mutations in the
atomic bomb survivors did not cause anyone to question the central role of DNA hits in producing
radiation effects. Non-targeted effects were first documented by Murphy and Norton in 1915 who showed
that irradiation of one part of the body could result in effects in distant parts. Later reports by several
authors over the years showed clastogenic effects in vivo and ex vivo where irradiated plasma was added
to cell cultures or injected into syngeneic animals. Efforts to isolate the factors involved failed and this
may explain why NTE did not become mainstream. Another issue was the difficulty of defining and
measuring endpoints at low radiation doses where these effects predominate. NTE really came to be
accepted during the 1990’s following critical contributions from our own laboratory in Ireland in 1986 and
those of Little in the US and Wright in the UK in 1992. It is often said that there is a “right time” for a “new”
conceptual understanding to be born which makes sense of seemingly unrelated facts. In the case of NTE
it was surely the scientific macroenvironment which suddenly recognized the importance of the
microenvironment in biology that provided the much needed framework to allow incorporation of NTE
into radiobiology. This session will review various aspects of the NTE field and will question the role of
DNA in radiation response.
80 | P a g e
IRRADIATE YOUR TARGET DIRECTLY TO GET A RESPONSE
This very first "History Symposium, organized by the History committee of the Radiation Research Society,
will discuss the history and implications of non-targeted effects (NTE) which include bystander effects,
genomic instability and adaptive responses. The symposium will not only review the history but will assess
the impacts of the field on cherished paradigms in radiobiology such as the central role of DNA damage
and repair. The evolution of elegant tools including microbeams, which enable the precise study of NTE
will also be reviewed. Finally the SIT speaker will look at the future and discuss how the increasing
acceptance of the role of NTE in radiobiology is influencing modern radiobiological research.
(S2201) 100 years of bystander effects: you don’t need a DNA hit to get a response. Carmel Mothersill,
McMaster Univ, Hamilton, Canada
The last 20 years have seen what is usually referred to as a “paradigm shift” in radiobiology. This is actually
more of a “paradigm widening” than a shift because it recognizes non-targeted effects (NTE) such as
bystander effects and genomic instability as part of the response spectrum measurable after exposure of
a system to ionising radiation. As with all paradigms, the evidence for these effects was documented
almost as soon as radiation biology became a science. However due to the dominance of Muller’s fruit fly
mutation work in 1925, the emphasis was firmly placed on DNA damage as being the main way cells and
organisms were damaged by radiation. The publication of the “green pamphlet” in 1935 “On the Nature
of Gene Mutation and Gene Structure” - by the geneticist Nikolai Vladimirovich Timoféeff-Ressovsky
(1900-1981), the radiation physicist Karl Günther Zimmer (1911-1988) and the theoretical physicist Max
Delbrück (1906-1981), established target theory and left little conceptual space for the idea that hitting a
target was not necessary to produce an effect. Even the lack of heritable damage or mutations in the
atomic bomb survivors did not cause anyone to question the central role of DNA hits in producing
radiation effects. Non-targeted effects were first documented by Murphy and Norton in 1915 who showed
that irradiation of one part of the body could result in effects in distant parts. Later reports by several
authors over the years showed clastogenic effects in vivo and ex vivo where irradiated plasma was added
to cell cultures or injected into syngeneic animals. Efforts to isolate the factors involved failed and this
may explain why NTE did not become mainstream. Another issue was the difficulty of defining and
measuring endpoints at low radiation doses where these effects predominate. NTE really came to be
accepted during the 1990’s following critical contributions from our own laboratory in Ireland in 1986 and
those of Little in the US and Wright in the UK in 1992. It is often said that there is a “right time” for a “new”
conceptual understanding to be born which makes sense of seemingly unrelated facts. In the case of NTE
it was surely the scientific macroenvironment which suddenly recognized the importance of the
microenvironment in biology that provided the much needed framework to allow incorporation of NTE
into radiobiology. This session will review various aspects of the NTE field and will question the role of
DNA in radiation response.
80 | P a g e
