Page 363 - 2014 Printable Abstract Book
P. 363
in the brain. Nevertheless, it is well-known that radiation therapy (RT) causes significant neurocognitive
deficits in patients, including deficits in attention, concentration, memory and executive and visuospatial
functions. These effects are very bothersome for patients, the mechanisms of their occurrence are not
understood, and they may be related to the bystander effects. We analyzed the induction, mechanisms
and behavioral repercussions of bystander effects in the brain upon liver irradiation in a rat model. We
hypothesized that RT-like exposure of rat liver will lead to epigenetically-medicated bystander effects in
rat brain. To test our hypothesis we analyzed global DNA methylation patterns, and conducted deep-
sequencing-based transcriptome profiling of the prefrontal cortex (PFC) and hippocampus tissues of rats
upon liver irradiation. In parallel, we conducted a comprehensive neuroanatomical and behavioral
analysis. Here, we for the first time show that bystander effects occur in the PFC and hippocampus regions
upon liver irradiation; they manifest as altered gene expression and DNA damage, are associated with
neuroanatomical and behavioral changes, and are much more pronounced in females than in males. We
will present a new mechanistic model of the radiation-induced bystander effects in brain, and outline the
future translational potential of our findings.
(PS7-19) The radiation carcinogenesis paradox. Otto G. Raabe, PhD; University of California Davis, Davis,
CA
A comparative evaluation is described for two types of radiation carcinogenesis. Ionizing radiation
induced cancer from internally deposited radionuclides is analyzed with data from human studies for Ra-
226, and from laboratory animal studies for alpha radiation associated with Ra-228, Ra-226, Ra-224, Pu-
238, Pu-239, Th-228, Cf-252, Cf-249, and Am-241 and for beta radiation associated with Sr-90, Y-90, Y-91,
and Ce-144. Intake routes included ingestion, inhalation, and injection. Cancer induction risk associated
with protracted ionizing radiation exposure is observed to be a rather precise function of lifetime average
dose rate to the affected tissues rather than a function of cumulative dose. The lifetime effects are best
described by a three-dimensional average dose-rate/time/response relationship that competes with
other causes of death during an individual's lifetime. At low average dose rates the time required to induce
cancer may exceed the natural lifespan yielding a lifetime virtual threshold for radiation induced cancer.
In sharp contrast the Atomic Bomb Survivor Studies display a somewhat linear relationship of
proportionality between increased lifetime cancer rates and acute ionizing radiation exposures. Resolving
this paradox involves the conclusion that two completely different carcinogenesis mechanisms are
associated with these two types of exposures to ionizing radiation. These are induction of cancer in the
case of protracted exposures and promotion of carcinogenic processes in the case of acute exposures.
(PS7-20) The lysophosphatidic acid receptor 2 is a DNA damage response gene and accelerates DNA
damage repair. Andrea Balogh; Sue Chin Lee; Souvik Banerjee; Ruchika Gangwar; Radakrishna Rao;
Ramesh Ray; Louisa Balazs; and Gabor Tigyi, University of Tennessee Health Science Center Memphis,
Memphis, TN
Several small molecule radiomitigators act via the lysophosphatidic acid receptor subtype 2
(LPA2). LPA2 mediates radiomitigation via the inhibition of apoptosis and stimulation of prosurvival
kinases. We investigated the transcriptional regulation of lpa2 gene expression in response to ionizing
radiation using the IEC-6, a primary epithelial cell line from rat small intestine. Using qRT-PCR profiling the
361 | P a g e
deficits in patients, including deficits in attention, concentration, memory and executive and visuospatial
functions. These effects are very bothersome for patients, the mechanisms of their occurrence are not
understood, and they may be related to the bystander effects. We analyzed the induction, mechanisms
and behavioral repercussions of bystander effects in the brain upon liver irradiation in a rat model. We
hypothesized that RT-like exposure of rat liver will lead to epigenetically-medicated bystander effects in
rat brain. To test our hypothesis we analyzed global DNA methylation patterns, and conducted deep-
sequencing-based transcriptome profiling of the prefrontal cortex (PFC) and hippocampus tissues of rats
upon liver irradiation. In parallel, we conducted a comprehensive neuroanatomical and behavioral
analysis. Here, we for the first time show that bystander effects occur in the PFC and hippocampus regions
upon liver irradiation; they manifest as altered gene expression and DNA damage, are associated with
neuroanatomical and behavioral changes, and are much more pronounced in females than in males. We
will present a new mechanistic model of the radiation-induced bystander effects in brain, and outline the
future translational potential of our findings.
(PS7-19) The radiation carcinogenesis paradox. Otto G. Raabe, PhD; University of California Davis, Davis,
CA
A comparative evaluation is described for two types of radiation carcinogenesis. Ionizing radiation
induced cancer from internally deposited radionuclides is analyzed with data from human studies for Ra-
226, and from laboratory animal studies for alpha radiation associated with Ra-228, Ra-226, Ra-224, Pu-
238, Pu-239, Th-228, Cf-252, Cf-249, and Am-241 and for beta radiation associated with Sr-90, Y-90, Y-91,
and Ce-144. Intake routes included ingestion, inhalation, and injection. Cancer induction risk associated
with protracted ionizing radiation exposure is observed to be a rather precise function of lifetime average
dose rate to the affected tissues rather than a function of cumulative dose. The lifetime effects are best
described by a three-dimensional average dose-rate/time/response relationship that competes with
other causes of death during an individual's lifetime. At low average dose rates the time required to induce
cancer may exceed the natural lifespan yielding a lifetime virtual threshold for radiation induced cancer.
In sharp contrast the Atomic Bomb Survivor Studies display a somewhat linear relationship of
proportionality between increased lifetime cancer rates and acute ionizing radiation exposures. Resolving
this paradox involves the conclusion that two completely different carcinogenesis mechanisms are
associated with these two types of exposures to ionizing radiation. These are induction of cancer in the
case of protracted exposures and promotion of carcinogenic processes in the case of acute exposures.
(PS7-20) The lysophosphatidic acid receptor 2 is a DNA damage response gene and accelerates DNA
damage repair. Andrea Balogh; Sue Chin Lee; Souvik Banerjee; Ruchika Gangwar; Radakrishna Rao;
Ramesh Ray; Louisa Balazs; and Gabor Tigyi, University of Tennessee Health Science Center Memphis,
Memphis, TN
Several small molecule radiomitigators act via the lysophosphatidic acid receptor subtype 2
(LPA2). LPA2 mediates radiomitigation via the inhibition of apoptosis and stimulation of prosurvival
kinases. We investigated the transcriptional regulation of lpa2 gene expression in response to ionizing
radiation using the IEC-6, a primary epithelial cell line from rat small intestine. Using qRT-PCR profiling the
361 | P a g e
