Page 362 - 2014 Printable Abstract Book
P. 362
pressure. From the results found in the preliminary works using both SHR and SHRSP rats, the combination
of these two might be one of the most useful model animals for assessing relationships between CD risks
and radiation. Based on results obtained from these systems, a proposal and testing of novel hypotheses
on mechanisms of radiation-related CDs may now be possible.
(PS7-16) Investigation of time-dose relationships in the cellular response to ion irradiation with the
1
1
1;2
Local Effect Model. Lisa Herr ; Thomas Friedrich, Dr. ; Marco Durante, Prof. Dr. ; and Michael Scholz,
1
1
Dr. , GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany and Institut für
2
Festkörperphysik, TU Darmstadt, Darmstadt, Germany
In this contribution, an investigation of the time-dose relationship in the effectiveness of ion
radiation with respect to cell killing will be presented. In general, protracted or split irradiation leads to a
reduction of the effect as compared to the delivery of an acute dose. An assessment of this reduction is
of special importance for radiation protection in outer space where extremely low dose rates prevail or
for medical treatments where applied doses might be highly fractionated. For corresponding predictions,
the Local Effect Model (LEM) has been extended. It accounts for the dynamics of dose rate dependent
damage induction and cellular damage repair and follows a similar concept as already described for time-
dose relationships after photon radiation. Referring to this concept, the number of DNA double strand
breaks (DSB) in domains in the cellular nucleus, identifiable with DNA giant loops of about 2 Mbp size, is
decisive for the corresponding lethality. Two or more coexistent DSB (clustered DSB) imply a damage
enhancement and slower repair kinetics as compared to single, isolated DSB that are linked to a fast
component of repair. Thus, a temporal and spatial separation of the initial lesions e.g. by lowering the
dose rate and the spatial density of induced DSB generally entails increased cell survival probabilities.In
our presentation, LEM predictions of the dependence of the radiation effectiveness on the total dose, its
protraction time, the linear energy transfer and the species of the particles will be shown. Furthermore,
a comparison to experimental data will reveal the validity of the model. In summary, our results indicate
that the actual radiation quality and the total dose have a distinct impact on the existence and the
magnitude of a reduction of radiation effectiveness. In that respect, the constant dose rate reduction
factor commonly used in radiation protection represents rather an approximation for more complex
underlying dependencies.
(PS7-17) Radiation-induced bystander effects in the brain: epigenetic mechanisms underlie behavioral
1
1
1
1
outcomes. Anna Kovalchuk ; Richelle Mychasiuk ; Arif Muhammad ; S. Russell Hossain ; Yaroslav
2
1
1
1
2
Ilnytskyy ; Charles Kirkby ; Esmaeel Ghasroddashti ; Bryan Kolb ; and Olga Kovalchuk , University of
1
Lethbridge, Lethbridge, Canada and Jack Ady Cancer Centre, the Chinook Regional Hospital, AHS,
Lethbridge, Canada
2
Ionizing radiation (IR) can elicit molecular and cellular responses in bystander cells and tissues
that were not hit directly by it but rather received a distress signal from irradiated cells. IR-induced
bystander effects also manifest themselves in the whole-organism context whereby IR exposure of one
side of the animal’s body causes profound molecular changes in the shielded bystander parts.
Similarly, cranial irradiation can exert molecular changes in shielded somatic organs and gonads of
experimental animals. Currently very little is known about the existence and nature of bystander effects
360 | P a g e
of these two might be one of the most useful model animals for assessing relationships between CD risks
and radiation. Based on results obtained from these systems, a proposal and testing of novel hypotheses
on mechanisms of radiation-related CDs may now be possible.
(PS7-16) Investigation of time-dose relationships in the cellular response to ion irradiation with the
1
1
1;2
Local Effect Model. Lisa Herr ; Thomas Friedrich, Dr. ; Marco Durante, Prof. Dr. ; and Michael Scholz,
1
1
Dr. , GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany and Institut für
2
Festkörperphysik, TU Darmstadt, Darmstadt, Germany
In this contribution, an investigation of the time-dose relationship in the effectiveness of ion
radiation with respect to cell killing will be presented. In general, protracted or split irradiation leads to a
reduction of the effect as compared to the delivery of an acute dose. An assessment of this reduction is
of special importance for radiation protection in outer space where extremely low dose rates prevail or
for medical treatments where applied doses might be highly fractionated. For corresponding predictions,
the Local Effect Model (LEM) has been extended. It accounts for the dynamics of dose rate dependent
damage induction and cellular damage repair and follows a similar concept as already described for time-
dose relationships after photon radiation. Referring to this concept, the number of DNA double strand
breaks (DSB) in domains in the cellular nucleus, identifiable with DNA giant loops of about 2 Mbp size, is
decisive for the corresponding lethality. Two or more coexistent DSB (clustered DSB) imply a damage
enhancement and slower repair kinetics as compared to single, isolated DSB that are linked to a fast
component of repair. Thus, a temporal and spatial separation of the initial lesions e.g. by lowering the
dose rate and the spatial density of induced DSB generally entails increased cell survival probabilities.In
our presentation, LEM predictions of the dependence of the radiation effectiveness on the total dose, its
protraction time, the linear energy transfer and the species of the particles will be shown. Furthermore,
a comparison to experimental data will reveal the validity of the model. In summary, our results indicate
that the actual radiation quality and the total dose have a distinct impact on the existence and the
magnitude of a reduction of radiation effectiveness. In that respect, the constant dose rate reduction
factor commonly used in radiation protection represents rather an approximation for more complex
underlying dependencies.
(PS7-17) Radiation-induced bystander effects in the brain: epigenetic mechanisms underlie behavioral
1
1
1
1
outcomes. Anna Kovalchuk ; Richelle Mychasiuk ; Arif Muhammad ; S. Russell Hossain ; Yaroslav
2
1
1
1
2
Ilnytskyy ; Charles Kirkby ; Esmaeel Ghasroddashti ; Bryan Kolb ; and Olga Kovalchuk , University of
1
Lethbridge, Lethbridge, Canada and Jack Ady Cancer Centre, the Chinook Regional Hospital, AHS,
Lethbridge, Canada
2
Ionizing radiation (IR) can elicit molecular and cellular responses in bystander cells and tissues
that were not hit directly by it but rather received a distress signal from irradiated cells. IR-induced
bystander effects also manifest themselves in the whole-organism context whereby IR exposure of one
side of the animal’s body causes profound molecular changes in the shielded bystander parts.
Similarly, cranial irradiation can exert molecular changes in shielded somatic organs and gonads of
experimental animals. Currently very little is known about the existence and nature of bystander effects
360 | P a g e
